XIX. European Stroke Conference
Barcelona, Spain
25 - 28 May 2010
Ongoing Trials ESC Barcelona 2010
OAID:
1
ICONS: Identifying Continence OptioNs after Stroke
Background
Urinary incontinence following acute stroke is common, affecting between 40%-60% of people admitted to hospital. It is distressing for those affected, is related to poor outcome and is currently poorly managed in many cases.
Our research programme aims to develop, implement and explore the potential effectiveness and cost-effectiveness of a systematic voiding programme for the management of urinary incontinence after stroke in hospital. The programme will include bladder training and pelvic floor muscle training for patients who are cognitively able and prompted voiding for patients with cognitive impairments.
The programme is based on the UK Medical Research Council (MRC) framework for the evaluation of complex interventions.
Methods
Phase I: MRC Development phase
• An evidence synthesis of qualitative and qualitative literature on combined approaches to managing urinary incontinence post-stroke.
• A case study of the introduction of the systematic voiding programme algorithm in one stroke service in the North West of England.
Phase II: MRC Feasibility and piloting phase (Exploratory trial)
Phase II aims to test the interventions for preliminary evidence of effect and feasibility. The trial will use cluster randomisation at the level of the stroke service and involve twelve stroke services randomised to receive:
• Systematic voiding programme (n=4)
• Systematic voiding programme plus supported implementation (n=4)
• Usual care (n=4)
Patient recruitment for this phase will take place between October 2010 and June 2011.
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Thomas L et al
L.Thomas, University of Central Lancashire, Preston, UNITED KINGDOM
C.Watkins
University of Central Lancashire
Preston
UNITED KINGDOM
BFrench
University of Central Lancashire
Preston
UNITED KINGDOM
F.Cheater
Glasgow Caledonian University
Glasgow
UNITED KINGDOM
J.Booth
Glasgow Caledonian University
Glasgow
UNITED KINGDOM
B.Roe
Edge Hill University
Ormskirk
UNITED KINGDOM
C.Burton
Bangor University
Bangor
UNITED KINGDOM
M.Leathley
University of Central Lancashire
Preston
UNITED KINGDOM
C.Sutton
University of Central Lancashire
Preston
UNITED KINGDOM
E.McColl
Newcastle University
Newcastle upon Tyne
UNITED KINGDOM
K.Brittain
Newcastle University
Newcastle upon Tyne
UNITED KINGDOM
J.Gotaas
University of Central Lancashire
Preston
UNITED KINGDOM
B.Carter
University of Central Lancashire
Preston
UNITED KINGDOM
H.Rodgers
Newcastle University
Newcastle upon Tyne
UNITED KINGDOM
J.Barrett
Wirral University Teaching Hospital NHS Foundation Trust
Liverpool
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
2
International Study of Primary Angiitis of the CEntral nervous system (I-SPACE): a proposal
BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a rare, idiopathic vasculitis of the CNS. Current knowledge of PACNS is derived primarily from small, retrospective studies. Large multicentre prospective registries, (ex. International Study on Cerebral Vein and Dural Sinus Thrombosis) provide valuable insight into rare diseases. The objective of a PACNS registry is to better understand the clinical manifestations, imaging, histopathology, treatment and prognosis of PACNS.
METHODS: Adults diagnosed with PACNS (Calabrese and Mallek criteria) by site physicians within the last year will be approached to participate in the I-SPACE, an international multicentre, prospective registry. Baseline clinical data and investigation results will be collected using standardized, web-based case report forms as will therapeutic interventions, complications and relapses. Angiography, neuro-imaging and histopathology results will be reviewed centrally. New vessel-wall imaging techniques will also be explored.
RESULTS: This registry will include ≥20 international centres. Approximately 20 patients will be recruited per year for ≥5 years (≥ 100 patients). Patients will be followed for ≥1 year.
CONCLUSIONS: The I-SPACE data will help us reevaluate current knowledge of clinical, radiological and histopathological manifestations of PACNS and suggest optimal therapeutic approaches. To join the I-SPACE, please contact the authors: sylanthier@gmail.com.
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I-SPACE co-investigators
J.Kovitz-Lensch, Cerebrovascular Disease Centre, Division of Neurology, CHUM, and Faculty of Medicine, Université de Montréal, Montreal, CANADA
A.Y.Poppe
Cerebrovascular Disease Centre, Division of Neurology, CHUM, and Faculty of Medicine, Université de Montréal
Montreal
CANADA
R.Swartz
Division of Neurology, Sunnybrook Health Sciences Centre, and Faculty of Medicine, University of Toronto
Toronto
CANADA
A.Demchuk
Department of Clinical Neurosciences, Foothills Medical Centre, and Faculty of Medicine, University of Calgary
Calgary
CANADA
J.Putaala
Department of Neurology, Helsinki University Central Hospital
Helsinki
FINLAND
J.M.Ferro
Serviço de Neurologia, Hospital de Santa Maria, Universidade de Lisboa
Lisbon
PORTUGAL
I.Crassard
Service de Neurologie, Hôpital Lariboisière
Paris
FRANCE
A.de Windt
Unité Neurovasculaire, Hôpital Saint Philibert, Institut Catholique de Lille
Lille
FRANCE
C.Odier
Centre hospitalier Universitaire Vaudois
Lausanne
SWITZERLAND
P.Michel
Centre hospitalier Universitaire Vaudois
Lausanne
SWITZERLAND
S.Lanthier
Cerebrovascular Disease Centre, Division of Neurology, CHUM, and Faculty of Medicine, Université de Montréal
Montreal
CANADA
Ongoing Trials ESC Barcelona 2010
OAID:
3
The Effects of Dual-Tasks on Walking and Cardiovascular Functions in Subjects with Stroke.
Background: The aim of this study was to examine the effects of dual-tasks (with cognitive functions and physical performance) on walking and cardiovascular functions in stroke patients.Methods: Four male and one female stroke subjects with avarage age of 55.40+/-10.11 were included to this study. The data included demographics, orthotic support, hemiplegic side, additional disease, smoking habbits. Walking and dynamic balance were assessed with Time Up and Go (TUG) test. In order to assess the effects of dual-tasks TUG was done free, with Weschler Memory Scale (WMS) to analyze cognitive function (TUG-cog) and with Cup Carrying Performance Test to analyze physical performance (TUG-cup). In all three TUG tests; breath and heart rate, systolic and dyastolic pressures were recorded as soon as the tests finished, at 3rd and 5th minutes recovery periods. Results: While three of five subjects had right sided hemiplegia, two of them were left sided. Patients had stroke approximately 12.9+/-16.53 months. When the results of TUG tests were compared, we found that there was significant difference between TUG-free and TUG-cup tests (p<0.05) whereas there was not any difference between TUG-free and TUG-cog (p>0.05). There was not any difference in cardiovascular recovery for all TUG tests (p>0.05). Conclusions: The results of this study showed that dual-tasks were important for daily life and causes additional efforts in walking and balance abilities. In addition to this, walking with physical performance was more difficult than the walking with cognitive performance. The cardiovascular recovery after free walking, walking with cognitive functions and walking with physical performance were almost same. However it sholud be remembered that the distance of TUG test (3m) may not be enough to cause a load in the cardiovascular system. We concluded that, walking with dual-tasks should be included in rehabilitation programs of stroke patients.
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Effects
O.TELLI ATALAY, PAMUKKALE UNIVERSITY, DENIZLI, TURKEY
T.CAN
PAMUKKALE UNIVERSITY
DENIZLI
TURKEY
E.BASKAN
PAMUKKALE UNIVERSITY
DENIZLI
TURKEY
N.CETISLI KORKMAZ
PAMUKKALE UNIVERSITY
DENIZLI
TURKEY
Ongoing Trials ESC Barcelona 2010
OAID:
4
Stroke Telemedicine for Arizona Rural Residents Trial
Objective:
To establish a system for the prospective collection, recording, and analysis of telestroke trial patient consultation and care data for the purpose of quality measure assessment and improvement and benchmarking against other telestroke programs.
Design:
Prospective, interventional, treatment, open-label, active control, single group assignment, safety/efficacy trial. Sample size is 500 subjects.
Population Studied:
Consenting adult patients presenting to a participating rural emergency department within 12 hours of an acute stroke syndrome onset.
Intervention(s):
Two way site independent audio/video telemedicine system with DICOM and Smart Phone with teleradiology application
Outcome Measure(s):
Quality measures for telestroke consultations
Trial Status:
Oct 2008 to Dec 2009, 1 Primary Stroke Center (PSC) Hub, 7 vascular neurology investigators, 5 spoke hospitals, 55 emergency medicine investigators, 2 program managers, 3 information technology analysts, and 4 research coordinators participated. The network conducted 174 telestroke consultations. Symptom onset to ED arrival median 75 min, ED arrival to telestroke hotline activation median 28 min, telestroke hotline activation to return call median 1 min, consent signing to consult commencing median 14 min, consult start to treatment decision median 24 min, treatment decision to treatment administration median 18 min, symptom onset to thrombolysis administration median 165 min, ED arrival to thrombolysis administration median 92 min. Proportion arriving by EMS, 64%. Subjects received IV thrombolysis, 24%. Consultations were subjected to technical observations, 68%. Of those, 3% prevented decision making and 44% delayed decision making. The remainder were clinically inconsequential. ED admitting diagnosis ischemic stroke, IV thrombolysis administration 24%, ischemic stroke, no IV thrombolysis administration 39%, Transient Ischemic Attack 7%, Intracranial Hemorrhage 10%, Not Cerebrovascular Disorder 11%, Unknown 9%. Patient status after ED: Admitted to spoke 64%, transferred to PSC 24%, non-PSC 1%, home 11%.
Study Duration:
3 years of subject accrual and 3 months for follow-up
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STARR Trial Coordinators and Investigators
B.Demaerschalk, Mayo Clinic, Phoenix, USA
D.Channer
Mayo Clinic
Phoenix
USA
TKiernan
Mayo Clinic
Phoenix
USA
B.Bobrow
Maricopa Medical Center
Phoenix
USA
Ongoing Trials ESC Barcelona 2010
OAID:
5
Baseline characteristics of the ROCKET AF study: comparison with recent atrial fibrillation studies
Background: Atrial fibrillation (AF), the most common cardiac arrhythmia, increases the risk of stroke. Warfarin is effective in reducing stroke risk but is burdensome and is difficult to control. Rivaroxaban is an oral, once-daily (od), direct Factor Xa inhibitor.
Methods: ROCKET AF is a randomized, double-blind, double-dummy, event-driven trial, comparing rivaroxaban with warfarin in patients with AF who have a history of stroke or at least two risk factors for future stroke. Patients are randomly assigned to receive rivaroxaban 20 mg od, or dose-adjusted warfarin titrated to a target international normalized ratio (INR) of 2.5 (range 2.0–3.0, inclusive) using point-of-care INR devices to receive true or sham INR values, depending on study drug allocation. The study is powered to show non-inferiority of rivaroxaban to warfarin for the composite of stroke and non-CNS systemic embolism (primary efficacy endpoint); and if demonstrated, superiority will be tested. The primary safety endpoint is the composite of major and clinically relevant non-major bleeding events. 14,269 patients were randomized from December 2006 until June 2009, and this event-driven trial will run for about 40 months.
Results: Baseline patient data from ROCKET AF and recent AF trials are shown in the Table.
Conclusion: ROCKET AF will determine the efficacy and safety of rivaroxaban compared with warfarin for the prevention of thromboembolism in a higher-risk set of patients with AF than enrolled in previous trials of novel agents.
Graphic: http://www.esc-archive.eu/barcelona10/graphics_barcelona/oaid_5.html
Table:
N/A
M.R.Patel, Duke Clinical Research Institute, Duke University, Durham NC, USA
R.C.Becker
G.Breithardt
W.Hacke
J.Halperin
G.Hankey
K.Mahaffey
C.Nessel
J.Paolini
J.Piccini
D.Singer
R.Califf
K.Fox
Ongoing Trials ESC Barcelona 2010
OAID:
6
A pivotal study evaluating the Ischemic Stroke System (ISS*) for treatment of Acute Ischemic Stroke up to 24 hours from stroke onset.
Background: A recent clinical pilot study (ImpACT-1), evaluated a novel device (the ISS) for the treatment of AIS in the anterior circulation up to 24 hours after stroke onset. The ISS contains an implantable neurostimulator (INS) designed to deliver stimulation to the sphenopalatine ganglion (SPG) situated outside the cranium. The open labeled pilot study compared 98 patients treated using the ISS to historical matched patients from the NINDS control arm. Results suggest that treatment is safe and efficacious (mean 90 day mRS score of patients is significantly lower (CMH test p = 0.001); 48% compared to 29% of patients demonstrated a favorable mRS outcome (mRS 0-2) (p=0.003).
Design: ImpACT-24 is a multinational pivotal study. It is a double blind sham control study. Patients are randomized to either ISS Stimulation or Sham Control in a 2:1 ration. 600 patients with AIS in the anterior circulation, baseline NIHSS 7-18 and ability to initiate treatment 8-24hrs from stroke onset will be enrolled. The ISS is implanted, to all patients, adjacent to the SPG through the greater palatine canal using a minimal invasive approach. ISS/sham stimulation is applied 4 hours daily for 5 consecutive days. Efficacy is assessed by mRS and NIHSS at 90 days. Safety is assessed by incidence of adverse events.
Results: To date, 128 patients have been enrolled. Mean age 68.9 yrs, mean treatment time from stroke onset 18 hrs, Median baseline NIHSS 12.1 (range 7-18). Mortality and SAE rates (14% and 25.7% respectively) are within the expected range.
Conclusion: ImpACT-24 is a multinational, randomized, double blind study with sham control (2:1) based on a clinical pilot study. It is designed to assess the effectiveness and safety of a novel device (ISS) for the treatment of AIS in a much needed broader therapeutic window than currently available.
* CAUTION — Investigational device. Limited by Federal (or United States) law to investigational use.
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NCT 00826059
C.A.Molina, Hospital Universitari Vall d’Hebron, Barcelona, SPAIN
Ongoing Trials ESC Barcelona 2010
OAID:
12
Development of Modified Venturi Mask Adjuvant Oxygen Therapy in Severe Acute Stroke Management
Background and Purpose: The effect of oxygen therapy in acute ischemic stroke remains undetermined. We seek to investigate the feasibility of adjuvant therapy with Venturi mask (VM) in acute severe cerebral infarction patients.
Methods: This is a multi-center single blind randomized case-control study testing the efficacy of an modified VM developed by the study team. Patients with NIHSS more than 15 and prestroke modified Rankin Scale (mRS) less than 2 will be screened within 48 hours after onset. Patients will be allocated to receive VM FiO2-40% or nasal cannula (NC) 5 L/min as the control group at a 2:1 ratio. The treatment duration will be 10 days. NIHSS, mRS, Barthel Index and all kinds of adverse events will be evaluated and follow-up on Day 1, 10, 21, 30 and every 30th day till Day 180. Concomitant medications will be not restricted.
Expected results: The primary outcome will be the NIHSS at 6 months which was thought to be 20 at VM group and 22 at NC. One hundred and fifty acute stroke patients will be recruited during the 1.5 years study period. This study would provide 80% power and a 5 % two-sided probability of a type I error for a test of the difference of 10% difference of NIHSS of VM and NC group at 6 months. Secondary outcomes will be the mortality, length of stay and the incidence of all kinds of adverse events. The mortality rate within 6 months was expected as 10% (8-12) in VM FiO2-40% group and 20% (16-24%) in NC.
Anticipated discussions: This study will test the beneficial effect of supplemental oxygen therapy in acute large ischemic stroke patients by modified VM.
Funding source: 98-Cli-011 DOH Taiwan
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CGMH
I.S.Wu , Chang Gung Memorial Hospital, Kaohsiung, Taiwan., Kaohsiung, TAIWAN
K.C.CHANG
Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Kaohsiung
TAIWAN
E.H.CHIU
Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Kaohsiung
TAIWAN
T.I.PENG
Chang Gung Memorial Hospital, Keelung, Taiwan.
Keelung
TAIWAN
T.H.LEE
Chang Gung Memorial Hospital, Linko, Taiwan.
Linko
TAIWAN
J.D.LEE
Chang Gung Memorial Hospital, Jiayi, Taiwan.
Jiayi
TAIWAN
Y.C.HUANG
Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Kaohsiung
TAIWAN
Ongoing Trials ESC Barcelona 2010
OAID:
15
Cerebral small vellel disease –a new epidemic in acute ischemic stroke. A study in native Norwegians and non-Western immigrants.
In recent studies, cerebral small vessel disease is the cause of ischemic stroke in an increasing amount of cases (up to 42%). Such lacunar infarcts are clinically characterized by pure motor or pure sensory neurological symptoms.
Non-Western immigrants are at particular risk of developing cerebral small vessel disease, probably due to a high prevalence of the metabolic syndrome in this group. Diagnosing an acute lacunar infarct may be challenging, especially since MRI rarely is available in the acute setting. Consequently, supplementary diagnostic instruments, such as ultrasound techniques, are of clinical interest. Thrombolytic treatment is a routine treatment in patients with ischemic stroke; still, it is not clear whether patients with small vessel disease have an ischemic penumbra that can be saved through thrombolysis.
Recurring lacunar infarcts may lead to cognitive impairments, and possibly to neurodegenerative clinical deficits such as positive primitive reflexes and extrapyramidal symptoms. It is not known whether these neurodegenerative clinical symptoms are associated with cognitive deficits or dementia.
In 200 patients (of whom at least 50 must be Non-Western immigrants) with acute cerebral small vessel disease, we want to evaluate the ischemic penumbra, the benefits of transcranial ultrasound techniques, clinical neurodegenerative findings and poststroke general functioning in Non-Western immigrants.
Aims of the study:
In patients with acute lacunar stroke, we want to evaluate:
1. Whether these patients have a penumbra zone surrounding the core of the infarct
2. Whether these patients have increased resistance in the middle cerebral artery (measured by duplex ultrasound)
3. The prevalence of clinical neurodegenerative findings (primitive reflexes and extrapyramidal findings)
4. Whether such clinical neurodegenerative findings are related to cognitive impairments
5. Life quality including cognitive and emotional impairments in Non-Western immigrants
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A.K.Knudsen, Dpt. of Neurology, Oslo University Hospital; Norway, Oslo, NORWAY
A.Reichenbach
Dpt. of Neurology, Oslo University Hospital, Norway
Oslo
NORWAY
J.A.Zwart
Dpt. of Neurology, Oslo University Hospital, Norway
Oslo
NORWAY
P.Nakstad
Dpt. of Neuroradiology, Oslo University Hospital, Norway
OSLO
NORWAY
B.Fure
Dpt. of Geriatric Medicine, Oslo University Hospital, Norway
Oslo
NORWAY
Ongoing Trials ESC Barcelona 2010
OAID:
16
Successful Implementation of Early Supported Discharge Services. Collaborative Leadership in Applied Health Research and Care (CLAHRC), Nottinghamshire, Derbyshire, Lincolnshire, UK.
Introduction
A recent Cochrane systematic review demonstrated that Stroke Early Supported Discharge (ESD) services can reduce long term dependency and admission to institutional care as well as reducing the length of hospital stay. No adverse impact on the mood or well-being of patients or carers was reported. This ongoing study aims to facilitate and evaluate the successful implementation of ESD services across Nottinghamshire, Derbyshire and Lincolnshire, UK. This study is being conducted to ensure that the health and cost benefits are still in evidence when ESD services are implemented into local areas.
Methods
We are in the process of conducting a modified Delphi technique with ESD trialists to reach expert consensus on the component parts of successful ESD implementation. Our aim is to promote the use of recommendations derived from research findings to facilitate successful implementation of ESD services across the region. We will evaluate whether benefits of ESD outlined in the research literature are evident in practice. ESD team models will be studied. We will also evaluate activities of daily living, mood and quality of life of patients who are admitted to ESD services and eligible patients who are not. Cost effectiveness data will also be captured.
Conclusion
The findings from our research will help inform the set up and delivery of evidnce based ESD services in the UK and abroad.
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R. Fisher, M. Walker et al;
R.Fisher, University of Nottingham, Nottingham, UNITED KINGDOM
M.Walker
University of Nottingham
Nottingham
UNITED KINGDOM
FNouri
University of Nottingham
Nottingham
VENEZUELA
MKerr
University of Nottingham
Nottingham
UNITED KINGDOM
AMoody
University of Nottingham
Nottingham
UNITED KINGDOM
HSayers
University of Nottingham
Nottingham
UNITED KINGDOM
R.McDonald
University of Nottingham
Nottingham
UNITED KINGDOM
K.Gaynor
Nottingham University Hospitals NHS Trust
Nottingham
UNITED KINGDOM
D.Good
Nottingham University Hospitals NHS Trust
Nottingham
UNITED KINGDOM
O.Newell
University of Nottingham
Nottingham
UNITED KINGDOM
P.Langhorne
University of Glasgow
Glasgow
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
18
NIHSS performed by nurses in a stroke unit
Author details:
Mari Johanne Bjerke, Stroke nurse, Edda Finnsdottir, Stroke nurse, Brynjar Fure MD, PhD, Margrete Mangset, PhD.
Department of Geriatric Medicine, Oslo University Hospital, Norway
Background:
The National Institutes of Health Stroke Scale (NIHSS) is a systematic 11 point evaluation tool, used to assess neurological deficits in patients with acute stroke. NIHSS is also used to identify clinical findings that might put the patient at risk for complications, and to support medical decisions. The reliability of the NIHSS performed by trained neurologists in clinical trials of acute stroke has been established in several hospital-based studies. However, it also has the potential to be used by nurses. We hypothesise that NIHSS done by nurses during the acute phase will enhance the quality of care for stroke patients.
Methodes:
Approximately 250 patients, consecutively admitted to the stroke unit at Oslo University Hospital, Ullevaal, will be included.
Using the NIHSS, all patients will be assessed by two neurologists and two nurses in the stroke unit. The interrater reliability of the observations will be assessed using kappa statistics.
To evaluate the patients’ experience, we will use a qualitative method, involving a semi-structured interview of five patients.
Purpose:
We aim to establish the reliability of the NIHSS performed by nurses in a Scandinavian stroke unit. If nurses can execute the NIHSS with the same quality as neurologists, this will enhance the quality of the monitoring of stroke patients, especially in the hyperacute setting when reperfusion therapies are administered. We also want to evaluate the patients’ experience regarding the care given during the testing situation.
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M.J.Bjerke, Stroke Unit, Department of Geriatric Medicine, Oslo University Hospital, Ullevaal, Oslo, NORWAY
E.Finnsdottir
Stroke Unit, Department of Geriatric Medicine, Oslo University Hospital, Ullevaal
Oslo
NORWAY
M.Mangset
Stroke Unit, Department of Geriatric Medicine, Oslo University Hospital, Ullevaal
Oslo
NORWAY
B.Fure
Stroke Unit, Department of Geriatric Medicine, Oslo University Hospital, Ullevaal
Oslo
NORWAY
Ongoing Trials ESC Barcelona 2010
OAID:
19
The Insulin Resistance Intervention after Stroke (IRIS) Trial
Among patients who survive an ischemic stroke or TIA, major sources of morbidity and mortality are
recurrent stroke and myocardial infarction (MI). New preventive therapies are needed. The IRIS trial will test a therapy based on evidence linking insulin resistance to increased risk for stroke and other vascular diseases. Insulin resistance affects a majority of stroke and TIA patients and is effectively modified with thiazolidinedione drugs used to treat type 2 diabetes. In addition to reducing insulin resistance,these drugs improve endothelial function, reduce vascular inflammation, promote fibrinolysis, improve lipids, and potentially prevent atherosclerosis.The IRIS trial will randomize 3,136 patients with insulin resistance (HOMA>3) TIA or stroke to pioglitazone or placebo. The follow-up for the trial is 4 years, on average. The primary outcome is stroke or MI. Secondary aims will evaluate the effect of piolgitazone on the prevention of diabetes and cognitive decline.
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The IRIS Investigators
K.L.Furie, Massachusetts General Hospital, Boston, USA
C.M.Viscoli
Yale University
New Haven
USA
L.H.Young
Yale University
New Haven
USA
M.J.Gorman
Univ. Vermont
Burlington
USA
S.E.Inzucchi
Yale University
New Haven
USA
R.I.Horwitz
Stanford Univ
Stanford
USA
A.M.Lovejoy
Yale University
New Haven
USA
W.N.Kernan
Yale University
New Haven
USA
Ongoing Trials ESC Barcelona 2010
OAID:
21
Bringing the Hospital to the Patient: Stroke Treatment directly at the Emergency Site
Silke Walter1, Panagiotis Kostpopoulos1, Anton Haass1, Iris Grunwald2, Panagiotis Papanagiotou3, Christian Roth3, Darius Kubulus4, Yang Liu1, Thomas Volk4, Wolfgang Reith3, Klaus Fassbender1.
1Department of Neurology, University Hospital of the Saarland, Homburg, Germany;
2Acute Vascular Imaging Centre, John Radcliffe Hospital, Oxford, England; 3Department of Diagnostic and Interventional Neuroradiology and 4Department of Anaesthesiology, Intensive Care and Pain Therapy, University Hospital of the Saarland, Homburg, Germany
Early treatment is critical for favorable outcome of acute stroke. Since implementation of rt-PA therapy within the narrow therapeutic window is difficult rt-PA thrombolysis is strongly underused. Acute stroke management needs to be reconfigured to allow rapid screening of eligible stroke patients for time-limited therapy. In this randomized, parallely assigning efficacy study (ClinicalTrials.gov Identifier: NCT00792220), we investigate whether a "Mobile Stroke Unit", a rescue car with an integrated CT scanner, point of care laboratory system and telemedicine contact to the hospital, necessary for a prehospital treatment of stroke, contributes to a better stroke management by saving precious time. Patients will be randomized to either one of two interventions: The Mobile Stroke Unit approach vs. an optimized conventional clinical management. Inclusion criteria are onset of symptoms until call of less that 2.5 h (and not after awakening) and clinical signs of stroke (Rossier stroke scale). Exclusion criteria are age below 18 and beyond 80, non-acute onset of symptoms, no focal stroke-like symptoms, pregnant patients. Primary outcome variable is the time between emergency call and therapy decision. Secondary Outcome variables: Time between emergency call and end of CT, end of blood analysis, start of thrombolysis, number of patients obtaining thrombolysis and functional status after 7 days. The study has been started monocentrically and will be opened to further centers.
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University Hospital of the Saarland, Germany
S.Walter, Department of Neurology, University Hospital of the Saarland, Homburg, GERMANY
P.Kostopoulos
Department of Neurology, University Hospital of the Saarland
Homburg
GERMANY
A.Haass
Department of Neurology, University Hospital of the Saarland
Homburg
GERMANY
P. Papanagiotou
Department of Diagnostic and Interventional Neuroradiology, University Hospital of the Saarland
Homburg
GERMANY
C.Roth
Department of Diagnostic and Interventional Neuroradiology, University Hospital of the Saarland
Homburg
GERMANY
I.Grunwald
Acute Vascular Imaging Centre, John Radcliffe Hospital
Oxford
UNITED KINGDOM
D. Kubulus
Department of Anaesthesiology, Intensive Care and Pain Therapy, University Hospital of the Saarland
Homburg
Y. Liu
Department of Neurology, University Hospital of the Saarland
Homburg
GERMANY
T.Volk
Department of Anaesthesiology, Intensive Care and Pain Therapy, University Hospital of the Saarland
Homburg
GERMANY
W.Reith
Department of Diagnostic and Interventional Neuroradiology, University Hospital of the Saarland
Homburg
GERMANY
K.Fassbender
Department of Neurology, University Hospital of the Saarland
Homburg
GERMANY
Ongoing Trials ESC Barcelona 2010
OAID:
24
VAST: Vertebral Artery Stenting Trial
Background: Twenty to 30 percent of all transient ischaemic attacks (TIA’s) and ischaemic strokes involve tissue supplied by the vertebrobasilar circulation. In about a quarter of the patients atherosclerotic stenosis >/= 50% of the vertebral artery accounts for vertebrobasilar stroke or TIA. The risk of recurrent vascular events in patients with vertebral artery stenosis is uncertain and revascularisation is not frequently performed. Treatment of vertebral artery stenosis by percutaneous transluminal angioplasty has been introduced as an attractive treatment option. The safety and benefit of stenting as compared with best medical therapy alone remains to be elucidated in a randomised clinical trial.
Objectives: The primary aim of the Vertebral Artery Stenting Trial (VAST; ISRCTN29597900) is to assess whether stenting for symptomatic vertebral artery stenosis >/= 50% is both feasible and safe. A secondary aim is to assess the rate of new vascular events in the territory of the vertebrobasilar arteries in patients with symptomatic vertebral artery stenosis >/= 50% on best medical therapy with or without stenting.
Design: This is a randomised, open clinical trial, comparing best medical treatment with or without vertebral artery stenting in patients with recently symptomatic vertebral artery stenosis. The trial will include a total of 180 patients with TIA or non-disabling ischaemic stroke that may be attributed to vertebral artery stenosis of at least 50%. The primary outcome is any stroke, vascular death, or non-fatal myocardial infarction within 30 days after start of treatment. Secondary outcome measures include any stroke or vascular death during follow-up and the degree of (re)stenosis after one year. As of April 2010, a total of 43 patients have been included.
Funding: Netherlands Heart Foundation, grant number 2007B045.
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H.B.van der Worp, University Medical Center Utrecht, Utrecht, THE NETHERLANDS
A.Compter
University Medical Center Utrecht. Rudolf Magnus Institute of neurosciences
Utrecht
THE NETHERLANDS
W.J.Schonewille
St Antonius Hospital
Nieuwegein
THE NETHERLANDS
A.Algra
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht
Utrecht
THE NETHERLANDS
J.Boiten
Medical Center Haaglanden
Den Haag
THE NETHERLANDS
G.J.Lycklama a Nijeholt
Medical Center Haaglanden
Den Haag
THE NETHERLANDS
P.J.Nederkoorn
Academic Medical Center Amsterdam
Amsterdam
THE NETHERLANDS
T.H.Lo
University Medical Center Utrecht
Utrecht
THE NETHERLANDS
W.P.Th.M.Mali
University Medical Center Utrecht
Utrecht
THE NETHERLANDS
F.L.Moll
University Medical Center Utrecht
Utrecht
THE NETHERLANDS
J.A. Reekers
Academic Medical Center Amsterdam
Amsterdam
THE NETHERLANDS
J.A.Vos
St Antonius Hospital
Nieuwegein
THE NETHERLANDS
L.J.Kappelle
University Medical Center Utrecht
Utrecht
THE NETHERLANDS
Ongoing Trials ESC Barcelona 2010
OAID:
25
The Interventional Management of Stroke (IMS) III Trial: An Ongoing Phase III Trial
BACKGROUND AND PURPOSE: The primary objective of this NIH-funded, Phase 3, randomized, multi-center, open-label clinical trial is to determine whether combined IV/IA approach to recanalization is superior to standard IV rt-PA alone when initiated within 3 hours of stroke onset.
METHODS: A projected 900 subjects with moderate-to-large (NIHSSS ≥10 or 8-9 with positive CTA and with a similar safety profile) ischemic strokes between ages 18-82 will be enrolled over 50 centers in the United States Canada Australia and Europe. Both approaches must have IV treatment initiated within 3 hours of stroke onset. Subjects will be randomized in a 2:1 ratio (IV/IA >IV).The IV rt-PA alone group will receive the full standard dose (0.9 mg/kg, 90 mg max [10% as bolus]) of rt-PA intravenously over an hour. The combined IV/IA group will receive a lower dose of rt-PA (~ 0.6 mg/kg, 60 mg max) over 40 minutes followed by immediate angiography. If a treatable thrombus is not demonstrated no IA therapy will be administered. If an appropriate thrombus is identified treatment will continue with one of the following: Concentric Merci® Retriever, the Penumbra System™, infusion of rt-PA with delivery of low-intensity ultrasound (the EKOS® Micro-Infusion Catheter) or infusion of rt-PA via standard micro-catheter. The choice of IA strategy will be made by the treating neurointerventionalist. IA treatment must begin within 5 hours and be completed within 7 hours of stroke onset. The primary outcome measure is a favorable clinical outcome, defined as a modified Rankin Score of 0-2 at 3 months. The primary safety measure is mortality at 3 months and symptomatic ICH within 36 hours after onset.
CONCLUSIONS: The IMS 3 Trial will develop and maintain a network of interventional centers to test the safety, feasibility and potential efficacy of new catheter devices as part of a combined IV/IA approach to recanalization as the IMS III Study progresses. As of April 6, 2010 371 subjects had been randomized.
Graphic:
Table:
for the IMS III Investigators
J.P.Broderick, University of Cincinnati Academic Health Center, Cincinnati, USA
T.A.Tomsick
University of Cincinnati Academic Health Center
Cincinnati
USA
Ongoing Trials ESC Barcelona 2010
OAID:
28
Secondary Prevention of Small Subcortical Strokes (SPS3)
Background Small subcortical strokes(S3) account for about 25% of all brain infarcts, are very frequent among Hispanic Americans(HA) and are usually due to cerebral small artery disease which predisposes to vascular dementia. Over 2 million S3 survivors are at high risk of stroke recurrence and subsequently vascular dementia; millions more suffer subclinical S3 and cognitive decline caused by the intrinsic disease of the small penetrating cerebral arteries. No previous randomized trials have focused on secondary prevention after S3 or subcortical TIA, optimal target levels of BP control after stroke and their relationship to cognitive decline, or prevention of stroke and dementia in HA. Objectives Determine: if the combination of Aspirin 325 mg/d+Clopidogrel 75 mg/d is more efficacious than Aspirin 325 mg/d alone AND whether intensive BP lowering (systolic <130 mmHg) is superior to usual hypertension management (systolic between 130-149 mmHg) in reducing stroke recurrence, cognitive decline and major vascular events in patients with symptomatic S3 or subcortical Transit Ischemic Attack (TIA). Methods SPS3 is a randomized multicenter clinical trial preceded by a 3 year pilot study. Patients are assigned in a factorial design to 2 interventions: a. Aspirin 325 mg/d vs. Aspirin 325 mg/d+Clopidogrel 75 mg/d. (double-blinded). b. Two targets of systolic BP, “usual” (130-149 mmHg) vs.“intensive” (<130 mmHg). (open-label with blinded event assessment).
Will include 3000 participants (20% HA) with symptomatic, MRI documented S3/subcortical TIA within the prior 6 months and without carotid stenosis or major cardiac sources of embolism. Follow-up every 3 months for a mean of 3.5 yrs. Outcomes Recurrent stroke (primary), cognitive decline, major vascular events and death. Trial Status 2650 patients from 8 countries are currently participating. The study will be completed on April 2012. Mean age is 63 yrs old; 63% Male; 25% Hispanics. Sponsorship NIH/NINDS. Registry # NCT00059306. Grant # U01 NS38529. http://www.sps3.org PI Oscar Benavente, MD. Professor of Neurology, University of British Columbia, Vancouver, Canada. Contacts Oscar.Benavente@ubc.ca; Hartr@uthscsa.edu
Graphic:
Table:
O. Benavente; R.Hart; A. Roldan; M. Benavente;
O.RBenavente, University of British Columbia, Vancouver, CANADA
A.Martin
Fundacion Idibell
Barcelona
SPAIN
M.Sanllorente
Fundacion Idibell
Barcelona
SPAIN
M.F.Benavente
University of British Columbia
Vancouver
CANADA
C.Coffey
University of Iowa
Iowa
USA
L.McClure
University of Alabama
Birmingham
USA
P.Pergola
University of Texas Health Science Center at San Antonio
San Antonio
USA
R.G.Hart
University of Texas Health Science Center at San Antonio
San Antonio
USA
Ongoing Trials ESC Barcelona 2010
OAID:
30
HAIST-NL: Hypothermia for Acute Ischaemic Stroke Trial - NL. A phase II randomised clinical trial
Background: Cooling to 32 - 34°C improves outcome in patients with post-anoxic encephalopathy after cardiac arrest. Animal studies strongly suggest that cooling also improves outcome after ischaemic stroke. In these studies, cooling was efficacious at temperatures of 35°C or below, with lower temperatures associated with a greater benefit. The feasibility of surface cooling to temperatures of 35°C or below in patients with acute ischaemic stroke has not been evaluated systematically.
Aim: To compare the feasibility and safety of surface cooling to 33, 34, and 35˚C, started within 4.5 hours after the onset of acute ischaemic stroke and maintained for 24 hours, in awake patients on a stroke unit.
Methods: This is a randomised, open, multi-centre, phase II clinical trial, comparing three different surface cooling strategies with standard treatment in 84 awake adult patients with acute ischaemic stroke and a score on the NIH Stroke Scale ≥ 6, admitted to a stroke unit. The trial consists of two phases. In the first, 48 patients will be randomised to conventional treatment (n = 12) or to surface cooling to 33, 34, or 35°C maintained for 24 hours (n = 12 in each group). In the second (validation) phase, 36 patients will be randomised to conventional treatment (n = 12) or to one of two surface cooling strategies selected from the first phase based on feasibility and safety (n = 12 in each group). The primary outcome measure is feasibility, defined as the number of patients that has successfully completed the treatment strategy they had been assigned to. Secondary outcome measures include safety and the score on the modified Rankin scale at three months. The trial is scheduled to start in August, 2010.
Discussion: This study will provide adequate information on the feasibility and safety of different surface cooling strategies on a stroke unit. It should facilitate the design of a large pragmatic phase III trial of surface cooling for acute ischaemic stroke.
Graphic:
Table:
HAIST investigators
M.Geurts, University Medical Centre Utrecht, Utrecht, THE NETHERLANDS
D.W.J.Dippel
Erasmus MC University Medical Center
Rotterdam
THE NETHERLANDS
G.J.Luijckx
University Medical Centre Groningen
Groningen
THE NETHERLANDS
A.Algra
University Medical Centre Utrecht
Utrecht
THE NETHERLANDS
L.J.Kappelle
University Medical Centre Utrecht
Utrecht
THE NETHERLANDS
H.B.van der Worp
University Medical Centre Utrecht
Utrecht
THE NETHERLANDS
Ongoing Trials ESC Barcelona 2010
OAID:
31
Third International Stroke Trial (IST-3). A large-scale randomised trial of thrombolytic therapy for patients with acute ischaemic stroke ISRCTN ISRCTN25765518
Background. Current regulatory approvals permit the use of thrombolysis in a highly selected subset of patients with acute ischaemic stroke. Objective. To determine whether a wider variety of patients can benefit from treatment than is possible under the current approvals. Design. IST-3 is a randomised controlled, trial of iv rt-PA (0.9mg/kg), with a PROBE (Prospective, Randomised, Open, Blinded Endpoint) design. Eligibility. acute ischaemic stroke, assessed and able to start treatment within 6 hours of onset, CT (or MR) scan has excluded intracranial haemorrhage. Details at www.ist3.com. Patient inclusion is by (telephone or a secure website to) a rapid centralised randomisation system balancing on key prognostic factors. Treatment is allocated after the baseline data have been recorded and cross-checked. Brain imaging (CT or MR) must be repeated after treatment (at 24-48hrs). In centres where pre-treatment perfusion or angiography are routine, these scans are collected as well the plain CT or MR scans. Baseline and follow-up CT/MR images reviewed by 'blinded' expert panel. Perfusion and angiography data are processed centrally. In all centres, follow-up is conducted by centralised (blinded) postal or telephone questionnaire, independently of the clinician treating the patient. Outcome measures: primary outcome is survival free of death or dependence at six months. Planned subgroup analyses: effect of: age, stroke severity, time to randomisation, blood pressure, CT appearances, perfusion or angiographic findings (where available) on the risks and benefits of treatment. Sample size With 3100 patients, the trial could detect a 4.7% absolute difference in the primary outcome. Trial Status: A total of 2178 patients had been recruited by 19th April 2010. Results will be reported in early 2012
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Table:
IST-3 collaborative Group
P.Sandercock, University of Edinburgh, Edinburgh, UNITED KINGDOM
RLindley
University of Sydney
Sydney
AUSTRALIA
J.Wardlaw
University of Edinburgh
Edinburgh
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
32
STARS trial, Stroke Treatment with Acute Reperfusion and Simvastatin
Background: A number of experimental studies have shown a neuroprotective role of statins in acute stroke studies by preventing increase in infarct volume and reducing hemorrhagic complications. MISTICS trial was a pilot, double-blind, randomized multicenter clinical trial which showed significant neurological improvement by the third day in patients receiving Simvastatin versus placebo, although with a non-significant increase in mortality rates and greater proportion of infections (OR 2.4, CI 95% 1.06 to 5.4) in the Simvastatin group.
Objectives: To determine whether Simvastatin treatment started within the first 12 hours from stroke onset improves neurological and functional outcomes, evaluated at the seventh day/discharge and at the third month. To demonstrate that Simvastatin is safe and not associated with higher rates of hemorrhagic transformations in patients receiving systemic thrombolysis.
Design: Multicenter, randomized, double-blinded, clinical trial controlled with placebo. A total of 340 patients will be randomized to either Simvastatin 40 mgrs once daily or placebo within the first 12 hours after symptoms onset. Treatment duration will be 3 months. Neurological status will be evaluated by means of NIHSS (National Institutes of Health Stroke Scale) score and functional outcome by means of modified Rankin scale scores at three months. A CT scan will be required to evaluate hemorrhagic transformations in patients receiving systemic thrombolysis.
Results: As of date April 2010, 20 patients have been included in 9 participating centers.
Funding: EC07/90195. ClinicalTrials.gov Identifier: NCT01073007.
Graphic:
Table:
STARS Trial Investigators
P.Delgado, Neurovascular Research Lab. Research Institute Vall Hebron, Barcelona, SPAIN
MRibó
Stroke Unit. Vall Hebron Hospital
Barcelona
SPAIN
C.Jimenez
Hospital Son Dureta
Palma de Mallorca
SPAIN
B.Vives
Hospital Son Dureta
Palma de Mallorca
SPAIN
D.Cànovas
Consorci Hospitalari Parc Taulí
Sabadell
SPAIN
A.Massot
Neurovascular Research Lab. Research Institute Vall Hebron
Barcelona
SPAIN
F.Muñoz
Hospital de Mollet
Mollet del Vallès
SPAIN
J.Krupinski
Hospital Mútua de Terrassa
Terrassa
SPAIN
F.J.De la Torre
Hospital Virgen del Rocío
Seville
SPAIN
MMFreijo
Hospital de Basurto
Bilbao
SPAIN
M.Martínez-Zabaleta
Hospital de Donostia
Donostia
SPAIN
T.Segura
Hospital de Albacete
Albacete
SPAIN
J.F.Arenillas
Hospital Universitario Valladolid
Valladolid
SPAIN
J.M.Flores
Hospital de Ciudad Real
Ciudad Real
SPAIN
J.Montaner
Neurovascular Research Lab and Stroke Unit Vall Hebron
Barcelona
SPAIN
Ongoing Trials ESC Barcelona 2010
OAID:
33
Induced Hypertension for Treatment of Delayed Cerebral Ischaemia after Aneurysmal Subarachnoid Haemorrhage.
Background: Delayed cerebral ischemia (DCI) is a major complication after aneurysmal subarachnoid haemorrhage (SAH), occurring in around 30% of patients and increasing case fatality 1.5 – 3 fold. Induced hypertension, alone or in combination with haemodilution and hypervolemia (Triple-H), is used around the world as a therapy in the treatment of DCI, but its efficacy in improving outcome is not based on a randomised clinical trial.
Objective: To investigate the outcome of induced hypertension versus no induced hypertension in patients with DCI after aneurysmal SAH.
Study design: A multi-centre, single blinded, randomized controlled trial.
Study population: Patients admitted after recent SAH with a treated aneurysm and DCI based on the onset of a new focal deficit and/or a decrease of the level of consciousness of at least 1 point on the Glasgow Coma Scale with exclusion of other causes of deterioration, will be randomized to either hypertension (n=120) or no hypertension (n=120).
Interventions: Patients in the intervention group will have their blood pressure raised with norepinephrine in order to improve cerebral blood flow. In case of a low cardiac output, dobutamin will be added. Induced hypertension will be continued for at least 48 hours when patients show some improvement within the first 24 hours. After 48 hours, the dose norepinephrine will be tapered daily, and resumed in case of clinical deterioration. In patients who do not show any improvement within 24 hours, of which at least 6 hours at a maximum dose, induced hypertension will not be continued.
Patients in the reference group will be treated according to the standardised SAH treatment protocol of the participating centre including oral nimodipine and normovolaemia without haemodilution.
Main outcome measurement: The modified Rankin scale at 3 months after the SAH, will be compared between patients who were randomized to induced hypertension and patients who were randomized to no induced hypertension.
Graphic:
Table:
C.S. Gathier, A.J.C. Slooter, G.J.E. Rinkel
C.S.Gathier, Department of Neurology/ Intensive Care, University Medical Centre Utrecht, Utrecht, THE NETHERLANDS
W.M.van den Bergh
Department of Intensive Care, Amsterdam Medical Centre
Amsterdam
THE NETHERLANDS
G.N.Beute
Department of Neurosurgery, St. Elisabeth hospital
Tilburg
THE NETHERLANDS
C.M.F.Dirven
Department of Neurosurgery, Erasmus Medical Centre
Rotterdam
THE NETHERLANDS
J.Horn
Department of Intensive Care, Amsterdam Medical Centre
Amsterdam
THE NETHERLANDS
M.Van der jagt
Dept of Intensive Care, Erasmus Medical Centre
Rotterdam
THE NETHERLANDS
F.van Kooten
Dept of Neurology, Erasmus Medical Centre
Rotterdam
THE NETHERLANDS
A.W.Oldenbeuving
Department of Intensive Care, St. Elisabeth hospital
Tilburg
THE NETHERLANDS
L.Regli
Department of Neurosurgery, University Medical Centre Utrecht
Utrecht
THE NETHERLANDS
G.Roks
Deptartment of Neurology, St. Elisabeth hospital
Tilburg
THE NETHERLANDS
W.P.Vandertop
Department of Neurosurgery, Amsterdam Medical Centre
Amsterdam
THE NETHERLANDS
B.H.Verweij
Department of Neurosurgery, University Medical Centre
Utrecht
THE NETHERLANDS
A.Algra
Julius Centre, Health Sciences and Primary care, University Medical Centre Utrecht
Utrecht
THE NETHERLANDS
G.J.E.Rinkel
Department of Neurology, University Medical Centre Utrecht
Utrecht
THE NETHERLANDS
A.J.C.Slooter
Department of Intensive Care, University Medical Centre Utrecht
Utrecht
THE NETHERLANDS
Ongoing Trials ESC Barcelona 2010
OAID:
34
‘Stem-cell Trial of recovery EnhanceMent after Stroke 2’ (STEMS2). Randomised placebo-controlled trial of granulocyte-colony stimulating factor in mobilising bone marrow stem cells in sub-acute stroke.
Background: Loss of motor function is common after stroke and often leads to significant long-term disability in spite of rehabilitation measures. Pre-clinical work suggests that transplantation of bone marrow stem cells into the brain improves motor recovery in experimental models of stroke. Peripheral blood stem cells (PBSCs) can be mobilised into the circulation using granulocyte-colony stimulating factor (G-CSF), an approach that has been found to be effective in experimental stroke. We have recently completed a phase IIa dose-escalation trial of G-CSF in 36 patients with sub-acute ischaemic stroke; G-CSF was effective in mobilising PBSCs and administration appeared to be safe and feasible.
Design: We hypothesise that G-CSF mobilised PBSCs in patients with recent stroke will migrate to the brain and promote recovery. We are performing a randomised placebo-controlled trial of G-CSF (10µg/kg) (given subcutaneously for 5 days) in patients following stroke investigating its safety, and study potential mechanisms of action by which G-CSF might improve outcome after stroke, with an emphasis on its effects on bone marrow derived PBSCs and their fate in the brain. We will use magnetic resonance in an attempt to track labelled-PBSCs migration to the brain. If appropriate, recruits will also approached to consider brain donation for histology and immunohistochemistry. The trial is performed in compliance with the International Conference on Harmonisation Good Clinical Practice guidelines.
Trial Status: Recruitment started in July 2007 and we have reached the target of 60 patients. The trial is currently in the follow up phase and is funded by The Medical Research Council.
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Table:
P.M.W.Bath, Institution of Neuroscience, University of Nottingham, Nottingham, UNITED KINGDOM
T.J.England
Institution of Neuroscience, University of Nottingham
Nottingham
UNITED KINGDOM
D.Auer
Institution of Neuroscience, University of Nottingham
Nottingham
UNITED KINGDOM
M.Abaei
Institution of Neuroscience, University of Nottingham
Nottingham
UNITED KINGDOM
J.Lowe
Institution of Neuroscience, University of Nottingham
Nottingham
UNITED KINGDOM
N.Russell
Department of Haematology, University of Nottingham
Nottingham
UNITED KINGDOM
M.Walker
Institution of Neuroscience, University of Nottingham
Nottingham
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
39
The CHInese Medicine (MLC 601, NeuroAid®) Efficacy on Stroke recovery (CHIMES) Trial : Progress and Safety Update.
Background : Stroke is a leading cause of death and disability worldwide. Despite improvements in acute stroke treatment, many patients only make a partial or poor recovery. During the early days to weeks following stroke, repair spontaneously occurs and the neurobiology of these events suggests a number of therapeutic targets to further promote recovery. Traditional Chinese Medicine (TCM) is commonly used to enhance the recovery process after stroke in China but lacks a reliable evidence base. However, because TCM may be potentially beneficial with an encouraging safety profile, further clinical trials focused on stroke rehabilitation and repair are required.
Methods : MLC 601, a TCM widely used in China to improve recovery after stroke, has recently been shown to restore neurological and cellular function in animal models of stroke by processes involved in repair1. Previous clinical trials have shown that MLC601 shows good tolerability and superiority over another TCM in terms of neurological disability and functional outcome2. A large double blind randomized placebo controlled clinical trial is underway to further assess safety and efficacy3
Results : At the end of April 2010, 546 patients have been randomised (out of a planned total of 1100) from 14 sites in 4 countries. A DSMB Board Meeting held in October 2009 recommended continued recruitment. We assessed the safety of MLC 601 in acute stroke patients treated for 3 months in a Singaporean substudy of CHIMES. Longer term laboratory safety data shows no differences between MLC601 and placebo4.
Conclusions : The data confirms MLC601’s safety in acute stroke patients receiving a 3-month treatment. More sites are welcome to participate in this landmark study.
References :
1. Heurteaux C, et al. Neuropharmacology. (2010) 58:987-1001
2. Chen C, et al. Stroke (2009) 40:859-63
3. Venketasubramanian N, et al. Int J Stroke (2009) 4:54-60
4. Young SH, et al. Cerebrovasc Dis. (2010) 30:1-6
Graphic:
Table:
CHIMES Investigators
C.Chen, National University of Singapore, Singapore, SINGAPORE
Ongoing Trials ESC Barcelona 2010
OAID:
40
Evaluation of a new patient-centred clinical monitoring tool for measuring longer-term unmet needs after stroke (LUNS)
Introduction
LUNS is a 22 item questionnaire that aims to identify longer-term unmet needs of stroke patients living in the community and thereby enable monitoring of the care provided to them. It was developed through systematic literature reviews and an iterative process of qualitative interviews, preliminary psychometric testing, expert peer review and consumer feedback. The psychometric properties of the LUNS questionnaire are now being evaluated in a multi-centre study.
Methods
The study aims to recruit 950 patients in two phases from approximately 40 stroke units across England. Patients who have suffered a new stroke event, are cognitively intact, able to read and understand English, and likely to be discharged to their own homes after at least 3 days in hospital were eligible for Phase 1 (n=350). For phase 2 (n=600), eligibility criteria are as for Phase 1 with the exception that patients must spend at least 14 days in hospital before discharge home and patients who have cognitive impairment and/or cannot read and understand English (but have a carer who can read and understand English) are also included with proxy responses allowed. Patients complete the LUNS, General Health Questionnaire-12 (GHQ12), Frenchay Activities Index (FAI) and Short Form-12 (v2) (SF12) by post at 3 or 6 months post-stroke. A second questionnaire pack is sent 1-2 weeks after completion of the first.
Results
In phase 1, 204 (58%) patients completed both questionnaire packs. LUNS had good test-retest reliability (Spearman’s correlation 0.77, % agreement of items 78-98%), adequate internal consistency for group level use (Cronbach’s alpha 0.81) and acceptable concurrent validity with GHQ12, FAI and SF12 (Spearman’s correlations 0.52, -0.37 and -0.53 respectively).
Discussion
LUNS has adequate acceptability, reliability and validity in cognitively intact, English speaking patients at 3-6 months post stroke. Phase 2 is now ongoing to evaluate LUNS in a wider population of stroke patients.
Graphic:
Table:
LoTS care LUNS study team
K.Mellish, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UNITED KINGDOM
R.Shannon
Bradford Teaching Hospitals NHS Foundation Trust
Bradford
UNITED KINGDOM
M. Horton
University of Leeds
Leeds
UNITED KINGDOM
B.Bhakta
University of Leeds
Leeds
UNITED KINGDOM
A.Farrin
University of Leeds
Leeds
UNITED KINGDOM
J.Murray
University of Leeds
Leeds
UNITED KINGDOM
A.House
University of Leeds
Leeds
UNITED KINGDOM
J.Young
Bradford Teaching Hospitals NHS Foundation Trust
Bradford
UNITED KINGDOM
A.Forster
Bradford Teaching Hospitals NHS Foundation Trust
Bradford
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
41
Cluster randomised trial evaluation of a patient and carer-centred system of longer-term stroke care (LoTS care stroke system of care trial)
Background:
Longer-term recovery is poor for many stroke patients, and patients may become depressed and house-bound and their carers may be stressed and anxious. Despite recognition of the importance of the longer-term consequences of stroke, services addressing these needs remain poorly developed in the UK. The LoTS care stroke system of care trial aims to improve outcomes after stroke by addressing the longer-term needs of patients and carers.
Methods:
This cluster randomised, controlled trial is designed to evaluate the clinical and cost-effectiveness of a system of care for stroke patients and their carers living in the community. The system of care was developed following systematic reviews of the quantitative and qualitative stroke literature and through interviews with stroke patients and their carers. The resulting comprehensive framework represents the range of longer-term problems experienced by stroke patients and their carers, and comprises a structured assessment linked to evidenced-based treatment algorithms and reference guides contained in a manual. It is supported by training and is being delivered by health professionals undertaking a community–based liaison or co-ordinating role for stroke patients (termed ‘Stroke Care Co-ordinators’ (SCCs)). SCCs in the control arm are continuing to deliver their usual practice. The trial is in the recruitment phase and aims to recruit 800 patients (and their carers, if appropriate) in 32 stroke services across the UK. The primary outcome is patient psychological health measured using the General Health Questionnaire-12 at six months post-recruitment with final follow-up at twelve months. The secondary outcomes include patient functional health, psychological and functional outcomes for carers and analysis of cost-effectiveness.
Results:
Recruitment began in July 2009 and as at the end of April 2010, recruitment was at 242. Recruitment is expected to be complete in December 2010 with results expected in mid 2012.
Graphic:
Table:
LoTS care Stroke System of Care trial team
K.Mellish, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UNITED KINGDOM
K.Shorter
Bradford Teaching Hospitals NHS Foundation Trust
Bradford
UNITED KINGDOM
A.Fergusson
University of Leeds
Leeds
UNITED KINGDOM
I.Holloway
University of Leeds
Leeds
UNITED KINGDOM
A.Patel
Kings College London
London
UNITED KINGDOM
A.Farrin
University of Leeds
Leeds
UNITED KINGDOM
J.Murray
University of Leeds
Leeds
UNITED KINGDOM
J.Nixon
University of Leeds
Leeds
UNITED KINGDOM
J.Young
Bradford Teaching Hospitals NHS Foundation Trust
Bradford
UNITED KINGDOM
A.Forster
Bradford Teaching Hospitals NHS Foundation Trust
Bradford
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
42
Antiplatelet Therapy in Combination with Recombinant t-PA Thrombolysis in Ischemic Stroke (ARTIS): a randomized controlled trial.
Background
Thrombolysis with rt-PA is currently the only approved acute therapy for ischemic stroke. Resistance to fibrinolysis and re-occlusion after initial recanalization are determinants of thrombolytic therapy failure. Re-occlusion occurs in 20 - 34% after rt-PA treatment and is associated with poor functional outcome. Re-occlusion is probably caused by platelet activation. In acute myocardial infarction, the combination of acetylsalicylic acid (ASA, aspirin) and thrombolysis resulted in a better reduction of mortality compared to thrombolysis alone. Moreover, subgroup-analysis of patients already on antiplatelet treatment prior to rt-PA thrombolysis shows that this group of patients has a better as outcome compared to patients with no previous use of antiplatelet drugs.
Objective
The aim of the trial is to investigate whether immediate addition of antiplatelet therapy to rt-PA thrombolysis in ischemic stroke improves functional outcome at 3 months.
Design
Multicenter, phase III, prospective, randomized, open treatment with blind endpoint assessment (PROBE design).
Study population
Patients with acute ischemic stroke receiving intravenous rt-PA thrombolysis not using preceding antiplatelet drugs. In order to find a clinically relevant effect of 10% absolute risk reduction in poor outcome a sample size of 800 patients is required.
Intervention
Patients are randomized to receive 300mg acetylsalicylic acid intravenous within 1.5 hours after start of rt-PA treatment or standard care.
Outcome
Primary outcome will be poor functional outcome at 3 months, defined as dependency or death (modified Rankin score 3-6). Among secondary end points are symptomatic intracranial haemorrhages or serious systemic haemorrhages within 48 hours after randomization.
Trial status
The ARTIS trial started recruiting patients end of 2008. Currently, 37 participating centres are actively randomizing and 360 patients have been included so far.
Trial registration
Netherlands Trial Registration NTR822
Funding
Netherlands Heart Foundation: 2005B118
Graphic:
Table:
ARTIS Study Group
S.M.Zinkstok, Academic Medical Centre, University of Amsterdam, department of Neurology, Amsterdam, THE NETHERLANDS
J.Stam
Academic Medical Centre, University of Amsterdam, department of Neurology
Amsterdam
THE NETHERLANDS
M.Vermeulen
Academic Medical Centre, University of Amsterdam, department of Neurology
Amsterdam
THE NETHERLANDS
R.J.de Haan
Academic Medical Centre, University of Amsterdam, department of Clinical Biostatistics
THE NETHERLANDS
Y.B.Roos
Academic Medical Centre, University of Amsterdam, department of Neurology
Amsterdam
THE NETHERLANDS
Ongoing Trials ESC Barcelona 2010
OAID:
43
Training Caregivers After Stroke (TRACS)
Background: Stroke is a family illness generating considerable personal, financial and societal burdens. Caregivers’ central role is often given low priority in the management of stroke and there are missed opportunities for structured skills training. To address this need we are evaluating by cluster, randomised, controlled trial the effectiveness of a structured, competency-based training programme for caregivers of stroke patients returning home with stroke-related disabilities.
Methods: Thirty six stroke units in the UK were randomised into intervention or control groups using the stratification factors of geographical site and quality of care as defined by the key 12 indicator score of the National Stroke Audit. The multidisciplinary teams in the units randomised to the intervention group were trained to deliver the intervention which includes a number of carer training sessions, competency assessment and one follow-up visit. Units randomised to the control group continued to provide usual care as per National Guidelines.
In common with other stroke rehabilitation trials the primary outcome point is at six months with final follow-up at 12 months. The primary patient outcome is the Nottingham Extended ADL Scale (NEADL). Secondary patient outcomes include: Hospital Anxiety and Depression Scale (HADS); EQ-5D; Barthel Index; death; institutionalisation; re-admission; Stroke Impact Scale; Client Service Receipt Inventory (economic outcome). The primary caregiver outcome is the Caregivers Burden Scale and secondary outcomes include: intervention compliance; Frenchay activities index; HADS; EQ-5D; death; institutionalization; Client Service Receipt Inventory.
Progress: Recruitment completed at the end of January 2010 with a total of 930 patients and carers recruited. Follow-up will continue until February 2011 and the results are expected in the autumn of 2011.
Graphic:
Table:
TRACS trial team
A.Forster, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UNITED KINGDOM
UNITED KINGDOM
J.Monaghan
Bradford Teaching Hospitals NHS Foundation Trust
Leeds
UNITED KINGDOM
J.Young
Bradford Teaching Hospitals NHS Foundation Trust
Bradford
UNITED KINGDOM
L.Kalra
Kings College London
London
UNITED KINGDOM
M.Knapp
Kings College London
London
UNITED KINGDOM
A.Patel
Kings College London
London
UNITED KINGDOM
D.Smithard
Kings College London
London
UNITED KINGDOM
S.Anwar
University of Leeds
Leeds
UNITED KINGDOM
A.Farrin
University of Leeds
Leeds
UNITED KINGDOM
I.Holloway
University of Leeds
Leeds
UNITED KINGDOM
J.Nixon
University of Leeds
Leeds
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
44
Angiotensin Receptor Blockade in Acute Stroke: The Scandinavian Candesartan Acute Stroke Trial (SCAST).
Background: It has long been a controversy whether high blood pressure should be lowered in the acute phase of stroke. ACCESS (Stroke 2003;34:1699) suggested a beneficial effect of the angiotensin receptor blocker candesartan in the acute phase of stroke, but these findings need to be confirmed in new, large trials.
Methods: SCAST is a multi-centre, randomised, placebo-controlled and double-blind trial of candesartan in acute stroke. Patients presenting within 30 hours of stroke (ischaemic or haemorrhagic) and with systolic blood pressure ≥ 140 mmHg are randomly assigned to candesartan or placebo for 7 days (doses increasing from 4 to 16 mg once daily). The follow-up period is 6 months. Primary effect variables: i) Death or major disability at 6 months; ii) Vascular death, myocardial infarction or stroke during the first 6 months
Status: Patient recruitment was stopped on February 28th 2010. A total of 2,026 patients have been included at >100 centres in Norway, Sweden, Denmark, Belgium, Estonia, Finland, Lithuania, Poland and Germany. The final visit of the last patient will be in September 2010. Characteristics at baseline: Mean age 71 years; blood pressure 171/91 mm Hg; ischaemic stroke 85%; haemorrhagic stroke 15%.
Funding: Basic funding from Norwegian health authorities. Trial drugs and unconditional grants from AstraZeneca and Takeda. Participating centres receive a limited economical compensation.
Conclusion: SCAST is to date the largest trial of blood pressure lowering treatment in the acute phase of stroke, and the first large trial with an angiotensin receptor blocker for this indication.
Graphic:
Table:
SCAST
E.CSandset, Oslo University Hospital Ulleval, Oslo, NORWAY
G. Boysen
Bispebjerg Hospital
Copenhagen
DENMARK
D.Jatuzis
Vilnius University Santariskiu Klinikos Hospital
Vilnius
LITHUANIA
J.Korv
Tartu University Hospital
Tartu
ESTONIA
S.Lüders
St. Josefs Hospital
Cloppenburg
GERMANY
P.Richter
Institute of Psychiatry and Neurology
Warsaw
POLAND
R.O.Roine
Turku University Central Hospital
Turku
FINLAND
A.Terént
Uppsala University Hospital
Uppsala
SWEDEN
V.Thijs
University Hospital Leuven
Leuven
BELGIUM
E.Berge
Oslo University Hospital Ulleval
Oslo
NORWAY
Ongoing Trials ESC Barcelona 2010
OAID:
45
Hypothermia for Acute Ischaemic Stroke (HAIST-UK) – A Pilot Study
Introduction: Hypothermia is a candidate treatment for acute ischaemic stroke based on efficacy in animal studies and in other neurological conditions. Cooling is probably most efficacious with temperatures of 34°C or below, but such temperatures may not be tolerated well by awake patients on a stroke unit. The aim of HAIST-UK is to compare the feasibility and safety of surface cooling to 35°C or 33°C, started within 4.5 hrs after the onset of acute ischaemic stroke and maintained for either 12 hrs or 24 hrs. This study is part of the EuroHYP network of trials looking into the development of hypothermia as a therapeutic tool in ischaemic stroke.
Methods: 24 eligible patients will be randomised to: Control = standard care, A = 35°C for 12 hrs, B = 33°C for 12hrs, C = 35°C for 24hrs or D = 33°C for 24hrs. In all patients randomised to hypothermia, cooling will be initiated by the intravenous infusion of 20 ml/kg cooled normal saline (4°C) over 30 mins, followed by surface cooling using the Arctic Sun device. Shivering and discomfort will be prevented and if necessary treated with intravenous pethidine. At the end of the cooling period patients will be warmed at 0.3°C/hr until the oesophageal temperature is 36°C after which the device will be disconnected.
Trial Objectives:
• to compare the safety, feasibility and tolerability of hypothermia at various depths and duration
• to identify which peripheral temperature measurement (oesophageal, rectal, bladder or tympanic) best reflects brain temperature as measured by MRI spectroscopy
• to identify which panel of biomarkers, mRNA or DNA may be suitable for incorporation into a larger trial
• to assess the effect on infarct volume using CT or MRI at baseline and at day 7
• to assess the effect on stroke severity as measured by mRS, NIHSS and BI at baseline, 1 and 3 months
Conclusions: HAIST-UK which is funded by CHSS has commenced enrolment and is among a number of pilot studies aiding the design of a definitive Phase III trial.
Graphic:
Table:
on behalf of the EuroHYP Network
B.Colam, University of Edinburgh, Edinburgh, UNITED KINGDOM
M.Macleod
University of Edinburgh
Edinburgh
UNITED KINGDOM
O.Ahmad
University of Edinburgh
Edinburgh
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
46
The Third International Stroke Trial (IST-3) Perfusion and Angiography Study: Current Progress and Participation.
Introduction: MR and CT Perfusion (MRP, CTP) and Angiography (MRA, CTA) are increasingly used in clinical practice, but their role in stroke diagnosis and decisions prior to rt-PA therapy remain unclear, with wide variation in practice. There is little evidence from randomised trials.
IST-3 is a randomised controlled trial of rt-PA given up to six hours after acute ischaemic stroke. Minimum essential pre-randomisation imaging in IST-3 is plain CT or MR, but some IST-3 centres also do CTP/CTA or MRP/MRA. With additional funding we are performing detailed, centralised analysis to determine the role of perfusion and/or angiography imaging in predicting safety and efficacy of rt-PA.
Progress: We set up a Perfusion/Angiography Steering Group of interested collaborators and experts, established centralised analysis of perfusion/angiography data and guidance on image acquisition. Following feedback from the Perfusion/Angiography core panel, we are analysing 11 MRP and 9 CTP (quantitative and relative) perfusion parameters and thresholds. Angiography data are quantified using TIMI and MORI scores.
Recruitment: 17 centres in 7 countries are doing CTP/CTA and 18 centres in 8 countries doing MRP/MRA in IST-3. We have collected data on 183 patients, including: pre-randomisation, 57 CTP, 16 MRP; 70 CTA and 22 MRA; post-randomisation follow-up: 3 CTP, 8 MRP; 14 CTA and 66 MRA, indicating a preference for early CT, later MR in acute stroke.
IST-3 continues to recruit new centres. Please contact us if you are interested in joining the trial (www.ist3.com). Recruitment ends in 2011 with a target sample of 3100 in the main trial (2199 recruited on 06/05/2010) including as many as possible with CTP/CTA and MRP/MRA data.
Conclusion: The Perfusion and Angiography data collected in IST3 will allow an analysis of the role of these imaging procedures in predicting thrombolysis safety and efficacy in acute ischaemic stroke.
Graphic:
Table:
The IST-3 Perfusion and Angiography Collaboration
T.Carpenter, University of Edinburgh, Edinburgh, UNITED KINGDOM
J.M.Wardlaw
University of Edinburgh
Edinburgh
UNITED KINGDOM
P.A.G.Sandercock
University of Edinburgh
Edinburgh
UNITED KINGDOM
R.I.Lindley
University of Sydney
Sydney
AUSTRALIA
V.Murray
Karolinska Institutet
Stockholm
SWEDEN
A.Peeters
University of Liege
Liege
BELGIUM
R.von Kummer
University of Dresden
Dresden
GERMANY
M.Parsons
John Hunter Hospital
Newcastle
AUSTRALIA
A.Kobayashi
University of Warsaw
Warsaw
POLAND
A.von Heijn
Karolinska Institute
Stockholm
SWEDEN
M.Wintermark
University of Virginia
USA
S.Davis
University of Melbourne
Melbourne
AUSTRALIA
G.Donnan
University of Melbourne
Melbourne
AUSTRALIA
F .Chappell
University of Edinburgh
Edinburgh
UNITED KINGDOM
E.Sakka
University of Edinburgh
Edinburgh
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
47
Rehabilitation Trials within the Virtual International Stroke Trials Archive: VISTA-Rehab
Background: Stroke rehabilitation is complex: interventions aim to alter various domains of patient outcome such as body functions, activity and participation. As a consequence the design, development and conduct of randomised clinical trials in this area are challenging. We developed an archive of stroke rehabilitation trials (VISTA-Rehab) which can be accessed to model and design future rehabilitation studies.
Methods: We sought trials that had been conducted since 1998 in which at least 20 patients with a clinical diagnosis of stroke were randomised to receive an intervention or standard care. We required that an assessment of the severity of the stroke be carried out at baseline and final follow up, using a recognised impairment/activity limitation scale (such as the Functional Independence Measure, Barthel Index or Modified Rankin Scale). We imposed no time limit between stroke onset and intervention reflecting the long-term nature of stroke rehabilitation. We established a Steering Committee to oversee projects and publications and commenced recruitment of rehabilitation trials into this resource.
Results: As of May 2010, rehabilitation data are available for 8865 patients. We have also secured commitments for contribution of data from an additional 4 trials. Demographic data including age (median=74, IQR [65, 80]), gender (male=52%) and initial dependency (median baseline Barthel Index score= 16, IQR [9, 19]), are available. Outcome measures include the modified Rankin Scale, Barthel Index, Rivermead Motor Assessment, Fugl Meyer Assessment, General Health Questionnaire and Nottingham Extended Activities of Daily Living Scale.
Conclusion: VISTA-Rehab expands the Virtual International Stroke Trials Archive (VISTA) to include rehabilitation trials. Anonymised data can be used to examine questions specific to stroke rehabilitation and to generate novel hypotheses. Investigators are invited to contribute further datasets and/or to propose analyses using these data.
Graphic:
Table:
On Behalf of the VISTA-Rehab Steering Committee
M.Ali, Glasgow Caledonian University , Glasgow, UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
48
Expansion of the Virtual International Stroke Trials Archive (VISTA).
Background: The Virtual International Stroke Trials Archive (VISTA) is a resource of stroke clinical trial data that can be utilised for novel exploratory analyses. Investigations to date have resulted in 24 peer reviewed publications and 32 presentations at national and international conferences. Expansion of this resource includes the development of 6 subsections: VISTA-Acute (acute stroke), VISTA-Rehab (rehabilitation), VISTA-Prevention (secondary prevention), VISTA-ICH (intracerebral haemorrhage), VISTA-Plus (general stroke population data) and VISTA-STIR/MR STROKE (stroke imaging data).
Methods: We developed specific eligibility criteria for entry of acute stroke, rehabilitation, secondary prevention, intracerebral haemorrhage, imaging and general stroke population data into each subsection of VISTA. We established allied but separate Steering Committees, comprising founding members and contributing trialists to oversee use and dissemination of data, provide feedback on proposals and manuscripts. These Steering Committee members are also eligible for co-authorship on manuscripts based on VISTA analyses which utilised their anonymised data.
Results: Data are available for analyses on 28,131 patients with acute stroke, 8865 patients with rehabilitation outcomes, 6731 patients from the general stroke population, and 1774 patients with intracerebral haemorrhage. We have also secured commitments for contribution of 2 trials to VISTA-Prevention, 4 trials to VISTA-Rehab and 1 registry to VISTA-Plus. VISTA-STIR/MR STROKE, the result of our collaboration with the STroke Imaging Repository and MR Stroke Group, is in an early developmental stage. Recruitment to all subsections is ongoing.
Conclusion: The development of these new subsections expands VISTA to include a wider range of stroke data. This will influence the quality of research that can be conducted within the resource. We invite investigators to contribute data and/or to propose analyses that will make use of the anonymised data held in VISTA.
Graphic:
Table:
On Behalf of the VISTA Steering Committees
M.Ali, University of Glasgow, Glasgow, UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
49
Efficacy of Nitric Oxide in Stroke (ENOS) Trial - A Prospective Randomised Controlled Trial in Acute Stroke
Rationale: Acute hypertension is associated with a poor outcome after stroke. No large trials have assessed the effect of altering BP during the acute phase of stroke on outcome. We are testing whether nitric oxide, a multimodal molecule given as glyceryl trinitrate (GTN), is safe and effective in improving outcome after acute stroke. Furthermore, around half of all patients admitted with acute stroke are taking antihypertensive therapy immediately prior to the stroke. No data exist as to whether it is beneficial or safe to stop or continue this treatment during the acute phase.
Design: ENOS is a prospective, international, multicentre, randomised, parallel-group, blinded, controlled trial. 5,000 ischaemic or haemorrhagic stroke patients with systolic BP 140-220 mmHg, and within 48 hours of onset will be included. Subjects will be randomised to 7 days of single-blind treatment with transdermal GTN or control. Those patients taking prior antihypertensive therapy will also be randomised to continue or temporarily stop this for 7 days. ENOS is conducted over a secure internet site. The primary outcome is modified Rankin Scale at 90 days which is carried out by a blinded assessor. The analysis will be by intention to treat.
Trial status: As at 4th May, 2010, 1784 patients had been recruited from 101 centres (Australia, Canada, China, Egypt, Hong Kong, India, Malaysia, New Zealand, Philippines, Poland, Republic of Ireland, Romania, Singapore, Spain, Sri Lanka and UK). More centres welcome to join.
Funding: The Medical Research Council.
Contact information: http://www.enos.ac.uk , E-mail: enos@nottingham.ac.uk, Telephone: +44 (0)115 823 1770
Graphic:
Table:
Bath P M W, Ankolekar S, Hogg C, Utton S
P. M WBath, University of Nottingham, Division of Stroke, Clinical Sciences Building, Hucknall Road, Nottingham, UNITED KINGDOM
S.Ankolekar
University of Nottingham, Division of Stroke, Clinical Sciences Building, Hucknall Road
Nottingham
UNITED KINGDOM
C.Hogg
University of Nottingham, Division of Stroke, Clinical Sciences Building, Hucknall Road
Nottingham
UNITED KINGDOM
S.Utton
University of Nottingham, Division of Stroke, Clinical Sciences Building, Hucknall Road
Nottingham
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
50
CLOTS 3 - A randomised trial to establish the effectiveness of Intermittent Pneumatic Compression to prevent post stroke deep vein thrombosis (DVT)
Introduction:
About 10% of immobile patients with stroke will develop a proximal DVT detectable on compression duplex ultrasound in the first month. The recently completed CLOTS trials have established that graduated compression stockings (GCS) do not reduce the risk of post stroke DVT. Anticoagulation, with heparins or low molecular weight heparin, reduce the risk of DVT but this benefit is largely offset by a three fold increased risk of bleeding. Intermittent Pneumatic Compression (IPC) is effective in surgical patients. Small RCTs in stroke suggest it is feasible in stroke patients although there are insufficient data to justify its routine use. The CLOTS trial 3 aims to test IPC in immobile stroke patients.
Methods:
These are based on those of the CLOTS trial. Immobile patients admitted to hospital within 3 days of an acute stroke can be randomised into the trial. Simple baseline data are collected via telephone or the web and the patient is randomised to Routine care + IPC or Routine care alone. The primary outcome is the presence of DVT in the popliteal vein or more proximal vein detected on either Doppler ultrasound or venography within 30 days of randomisation. Patients have a screening Doppler ultrasound of both legs between Day 7 and Day 10 and between Day 25 and Day 30. Data are collected at hospital discharge to monitor compliance and to identify in hospital complications, deaths and length of stay. At six months we establish patient's place of residence, functional status, current antithrombotic medication regimen and the quality of life.
Conclusions:
Funding has been obtained by the by the NHS R&D Health Technology Assessment Board. The main phase of the trial started on 1st April 2010 and will include at least 50 UK centres and enrol over 2000 patients. The trial has recruited 230 patients in 32 centres. The trial has been adopted by the UKSRN.
Graphic:
Table:
On behalf of the CLOTS trial collaboration
M.S.Dennis, University of Edinburgh, Edinburgh, UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
51
Thrombolysis Or Anticoagulation for Cerebral venous Thrombosis (TO-ACT trial)
Background
Endovascular thrombolysis (ET) may be beneficial for a subgroup of patients with cerebral venous sinus thrombosis (CVT) who have a poor prognosis. Case series have shown promising results of ET, but there are no randomized controlled trials.
Objective
The TO-ACT trial aims to determine if ET improves functional outcome of patients with a severe form of CVT, as compared to standard treatment with heparin.
Study design
International, multi-centre, prospective, randomized, open-label, blinded endpoint (PROBE) trial. Embedded within the 2nd International Study on CVT (ISCVT-2).
Study population
Patients with radiologically proven CVT, a high probability of poor outcome (defined by presence of one or more of the following risk factors: mental status disorder, coma, intracranial hemorrhagic lesion or thrombosis of the deep cerebral venous system) and uncertainty of the responsible physician if ET or standard treatment is better.
Intervention
Randomized patients will receive either ET or standard therapy (heparin in therapeutic dose). ET consists of local application of rt-PA or urokinase within the thrombosed sinuses. Additional endovascular methods to mechanically remove clot material, such as thrombosuction, are allowed.
Endpoints
The primary endpoint is the modified Rankin scale (mRS) at 12 months. Secondary outcomes are the mRS at 6 months and recanalization rate. The principal safety outcome is the occurrence of major intra- and extracranial hemorrhagic complications. Assessment of study endpoints will be done by a blinded neurologist or research nurse, not involved in the treatment of the patient, using standardized questionnaires
Study size and timeframe
Patient recruitment will start in the second half of 2010. We aim to include 164 patients within 4 years.
Further information
Investigators who are interested and would like to participate may e-mail us at toact@amc.nl
Graphic:
Table:
J.M.Coutinho, Academic Medical Centre, Amsterdam, THE NETHERLANDS
J.Stam
Academic Medical Centre
Amsterdam
THE NETHERLANDS
J.M.Ferro
Hospital Santa Maria
Lisbon
PORTUGAL
M.-G.Bousser
Hôpital Lariboisière
Paris
FRANCE
P.Canhão
Hospital Santa Maria
Lisbon
PORTUGAL
I.Crassard
Hôpital Lariboisière
Paris
FRANCE
C.B.L.M.Majoie
Academic Medical Centre
Amsterdam
THE NETHERLANDS
J.A.Reekers
Academic Medical Centre
Amsterdam
THE NETHERLANDS
E.Houdart
Hôpital Lariboisière
Paris
FRANCE
R.J.de Haan
Academic Medical Centre
Amsterdam
THE NETHERLANDS
Ongoing Trials ESC Barcelona 2010
OAID:
52
A VERY EARLY REHABILITATION TRIAL (AVERT): ONGOING PHASE III TRIAL EFFICACY
& COST EFFECTIVENESS STUDY
Background: Getting patients out of bed very early after stroke may be an important component
of effective stroke unit care. Within a multi-centre, single blind, randomized controlled trial, we
hypothesize that very early mobilisation will reduce death and disability and be cost effective.
Methods: Medically stable patients within 24 hrs of stroke, first or recurrent, infarct or
haemorrhage, including those treated with rtPA are eligible. Patients with severe premorbid
disability are excluded. Randomisation is stratified by site and stroke severity. Intervention is
delivered by a nurse/physiotherapist team, commences within 24 hours of stroke and continues at
least twice daily until discharge or a maximum of 14 days. Control patients receive standard care.
Primary outcome: modified Rankin Scale at 3 months. Sample size is 2104 patients (n=1052 per
group). A cost effectiveness analysis forms part of the study design.
Trial status: Recruitment commenced in July 2006. Thirty five hospitals in Australia, New
Zealand, Singapore, Malaysia, Scotland, Northern Ireland, Wales and Canada now participate. At April 2010, 659 patients (~7% all admitted strokes) have been recruited. Subjects recruited have an average age 70 (SD13) years, 50% have moderate-severe stroke (NIHSS>7), 80% with their first stroke
and 90% were living at home prior to stroke. 16% have been treated with rtPA. Reasons for nonrecruitment include: (i) patients admitted > 24 hours after stroke (40%) and (ii) admitted after
hours/ weekends (28%) when there was no recruiter.
Conclusion: The trial is progressing well. Further expansion of trial sites in the UK following a recent Stroke Association grant should see recruitment completed by end of 2012.
Graphic:
Table:
on behalf of the AVERT Trialists Collaboration
J.M.Collier, Florey Neuroscience Institutes, Melbourne, AUSTRALIA
J.Bernhardt
Florey Neuroscience Institutes
Melbourne
AUSTRALIA
H.Dewey
Austin Health
Melbourne
AUSTRALIA
A.Thrift
Baker IDI Heart and Diabetes Institute
Melbourne
AUSTRALIA
R.Lindley
University of Sydney
Sydney
AUSTRALIA
G.Donnan
Florey Neuroscience Institutes
Melbourne
AUSTRALIA
P.Langhorne
University of Glasgow
Glasgow
UNITED KINGDOM
S.Lennon
University of Ulster
Co Antrim
UNITED KINGDOM
K.Md Ali
UKM Medical Centre
Kuala Lumpur
MALAYSIA
M.T.Ahmad
Singapore General Hospital
SINGAPORE
A.McRae
Auckland City Hospital
Auckland
NEW ZEALAND
M.Moodie
Deakin University
Melbourne
AUSTRALIA
O.Wu
University of Glasgow
Glasgow
UNITED KINGDOM
A.Cooper
Swansea University
Swansea
UNITED KINGDOM
M.Oredegbe
Medicine Hat Regional Hospital
Medicine Hat
CANADA
Ongoing Trials ESC Barcelona 2010
OAID:
53
Multi-centre randomised controlled trial of an outdoor mobility intervention after stroke: an on-going trial
Background
Up to 42% of stroke patients do not get out of the house as much as they would like leading to a reduction in quality of life. A single centre randomised controlled trial (Logan 2004) reported that a targeted outdoor mobility rehabilitation intervention resulted in significantly more people getting out of the house as much as they wanted to. However the intervention was provided by only two therapists in one geographical location. We therefore conducted a multi centre study to confirm these findings and establish the cost effectiveness.
Method
A multi centered randomised controlled trial will include 676 participants, over 18 years of age, who have had a stroke and wish to get out of the house more often. Participants will be randomly allocated to either the intervention group or the control group. Intervention group participants will receive up to 12 rehabilitation outdoor mobility sessions over 4 months. Control group participants will receive conventional intervention for outdoor mobility which consists of verbal advice and provision of leaflets provided over one session only. Outcome measures will be collected by postal questionnaires using independent assessors if required and monthly travel calendars. The primary outcome measure is the Social Function domain of the SF36 quality of life assessment six months after recruitment
Current Status
The trial is registered (Current Trials ISRCTN58683841), has ethical and UK NHS approval. It is supported by the UK Stroke Research Network, the Primary Care Research Network and the Comprehensive Research Network. Nine UK primary care sites are taking part in the trial. Therapists in each centre have been trained in the new outdoor mobility intervention following development of a standardised programme and manual. Participant recruitment started in November 2009 and will continue until April 2011. At present 72 participants have been recruited, 35 to the intervention group and 37 to the routine group.
Graphic:
Table:
Getting out of the House
P.A.Logan, University of Nottingham, Nottingham, UNITED KINGDOM
M.Leighton
University of Nottingham
Nottingham
UNITED KINGDOM
M.F.Walker
University of Nottingham
Nottingham
UNITED KINGDOM
J.R.F.Gladman
University of Nottingham
Nottingham
UNITED KINGDOM
S.Armstrong
University of Nottingham
Nottingham
UNITED KINGDOM
T.Sach
University of East Anglia
Norwich
UNITED KINGDOM
O.Newell
Service user
Nottingham
UNITED KINGDOM
A.Avery
University of Nottingham
Nottingham
UNITED KINGDOM
H.Williams
University of Nottingham
Nottingham
UNITED KINGDOM
K.O'Neil
Gateshead NHS Primary Care Trust
Gateshead
UNITED KINGDOM
A.McCluskey
University ofSydney
Sydney
AUSTRALIA
T.Baird
Tower Hamlets NHS Primary Care Trust
London
UNITED KINGDOM
D.Barer
Gateshead NHS Primary Care Trust
Gateshead
UNITED KINGDOM
J.Bisiker
Wolverhampton NHS Primary Care Trust
Wolverhampton
UNITED KINGDOM
S.Leach
Lincolnshire Primary Care Trust
Lincoln
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
54
Mesh Ablator versus Cryoballoon Pulmonary Vein Ablation of Symptomatic Paroxysmal Atrial Fibrillation (MACPAF) Study: Rationale and Design
Background: Catheter ablation of the pulmonary veins has become accepted as a standard therapeutic approach for symptomatic paroxysmal atrial fibrillation (AF). However, there is some evidence for an ablation associated (silent) stroke risk, lowering the hope to limit the stroke risk by restoration of rhythm over rate control in AF. The purpose of this prospective randomized single-center trial (MACPAF study; clinicaltrials.gov NCT01061931) is to compare the efficacy and safety of two balloon based pulmonary vein ablation systems in patients with symptomatic paroxysmal AF.
Methods: Patients are randomized 1:1 for the Arctic Front® or the HD Mesh Ablator® catheter for left atrial catheter ablation (LACA). The predefined endpoints will be assessed by serial brain magnetic resonance imaging (MRI), neuro(psycho)logical tests and a subcutaneously implanted reveal recorder for AF detection. According to applied statistics 108 patients will be enrolled.
Results: As of May 1st, 2010, 28 patients have been randomized and 24 underwent LACA.
Discussion: Results from MACPAF will provide important information helping cardiologists and neurologists to better counsel AF-patients concerning risks and benefits of LACA. Doing MACPAF, we hope to make a significant contribution to the evaluation of the LACA-associated (silent) stroke risk. Furthermore, we hope to set the stage for stroke-risk reduction by improved technical conditions and appropriate patient selection. Limitations of the study are the single-center design, the existence of a variety of LACA-catheters, the missing placebo-group and the impossibility to assess the primary endpoint in a blinded fashion.
Graphic:
Table:
MACPAF collaborators
K. G.Haeusler, Department of Neurology, Charité, Berlin, GERMANY
L.Koch
Department of Cardiology and Pneumology, Charité
Berlin
GERMANY
J.Ueberreiter
Department of Neurology, Charité
Berlin
GERMANY
M.Endres
Center for Stroke Research, Charité
Berlin
GERMANY
H.-P.Schultheiss
Department of Cardiology and Pneumology, Charité
Berlin
GERMANY
A.Schirdewan
Department of Cardiology and Pneumology, Charité
Berlin
GERMANY
J. B.Fiebach
Center for Stroke Research, Charité
Berlin
GERMANY
Ongoing Trials ESC Barcelona 2010
OAID:
55
Platelet Transfusion in Cerebral Haemorrhage
Background
Hematoma volume is one of the most important outcome predictors in intracerebral hemorrhage (ICH). At least 38% of patients suffer from hematoma growth which occurs mainly in the first 6 hours. If patients are selected carefully, outcome may be improved by limiting hematoma growth. The use of antiplatelet treatment (APT) seems to be a risk factor for the development of hematoma growth as well as poor outcome.
Objective
To investigate whether platelet transfusion in patients with ICH, who are using antiplatelet agents, improves outcome by preventing hematoma growth.
Design
PROBE design: Prospective, Randomized, Open treatment, Blinded Endpoint evaluation
Inclusion criteria
- Age 18 years or older
- Spontaneous, non-traumatic supratentorial ICH confirmed by CT scan
- GCS score 8-15
- Antiplatelet treatment in the week preceding ICH
- Treatment can start within 6 hrs after onset of symptoms
- Treatment can start within 1½ hrs after CT
- Pre-stroke mRS score 0 or 1
Exclusion criteria
- Suspected epidural, subdural, aneurysmal or AVM hematoma
- Surgical evacuation planned within 24 hrs
- Intraventricular extension
- Previous transfusion reaction
- Use of Vitamin K antagonists (Warfarin) in the previous 5 days
- Known thrombocytopenia < 100 x 109 /l
- History of coagulopathy
- Previously legally incompetence
- Death appears imminent
Sample size
Outcome is assessed with the mRS, a score of 4 or more is defined as poor outcome. If poor outcome is reduced from 0.70 to 0.50, 95 patients are required in each group, totalling 190 patients.
Primary endpoint
Poor outcome mRS 4-6 at 3 months
Main secondary endpoints
- Hematoma growth within 24 hrs
- Complications of platelet transfusion (thrombotic complications and transfusion reaction)
- Predictive value of the CTA "spot sign" regarding primary outcome
- Predictive value of the CTA "spot sign" regarding hematoma growth
- Patient’s functional health using the full ordinal scoring range of the mRS at 3 months
Graphic:
Table:
PATCH
K.de Gans, Academic Medical Centre, Amsterdam, THE NETHERLANDS
M.Vermeulen
Academic Medical Centre
Amsterdam
THE NETHERLANDS
Y.B.Roos
Academic Medical Centre
Amsterdam
THE NETHERLANDS
Ongoing Trials ESC Barcelona 2010
OAID:
56
Practical aspects and efficacy of warfarin therapy in cardioembolic stroke prevention
Background
New methods of cardioembolic stroke (CS) prevention get developed worldwide. The aim of the study is to evaluate practical aspects and efficacy of warfarin (Wn) therapy in CS primary and secondary prevention.
Methods
The trail is ongoing unicenter prospective. From December 2009 up till now had been analyzed 73 cases of acute stroke classified as CS according to SSS-TOAST criteria. First, clinical record analysis and attending neurologist’s inquiry were done. Then patient’s telephone inquiry was used to recognize patients` level of disability and incidence of primary outcome (death, myocardial infarction, stroke, systemic embolism, hospitalization for any cause) or hemorrhage within 30 days from the stroke onset.
Results
None of patients used Wn prior stroke. Main source of embolism was atrial fibrillation (AF) in 87,7% of cases. CHADS2 score in AF group was 2,4 +/-1,1. In 81.3 +/- 0.4% of cases CHADS2 score was >1. The correlation coefficient between CHADS2 score prior stroke and mRs was 0.456 (p<0.001).
Antiplatelet therapy (a/p) was recommended in 42,5% (31) (age=79,3+/- 6,7%, mRs=3.53+/-1,52), Wn in 56,2% (41) (age=73,7+/-7,3%, mRs=2,05+/-1,36) of cases at discharge. Contraindications for Wn were patient’s incompliance in 31,3% (10), INR control inaccessibility in 18.8% (6), hemorrhagic risk in 25% (8), severe disabling stroke in 25% (8).
Within 30 days there was: primary outcome in a/p group in 32,1% (9) (CI 17,9-50,6%), in Wn group in 4,0% (1) (CI 0,7-20,2%), major hemorrhage in a/p group in 0% (CI 0-12,1%), in Wn group 4,0% (1) (CI 0,7-20,2%), minor hemorrhage in a/p group in 0% (CI 0-12,1%), in Wn group 16,7% (1) (CI 6,7-35,9%) cases.
Conclusion
Wn is used extremely insufficiently for primary CS prevention. Wn is contraindicated after CS in almost half (43,8%) of cases and risk of hemorrhage isn’t the main contraindication. There is positive correlation between mRs at 30 days after stroke and CHADS2 score prior stroke.
Graphic:
Table:
Timcenko M. et al
M.Timcenko, Riga Stradins University, Riga, LATVIA
D.Volceka
Riga Stradins University
Riga
LATVIA
V.Kenina
Riga Stradins University
Riga
LATVIA
E.Miglane
Riga Stradins University
Riga
LATVIA
A.Millers
Riga Stradins University
Riga
LATVIA
P.Sipacovs
Pauls Stradins Clinical University Hospital
Riga
LATVIA
Ongoing Trials ESC Barcelona 2010
OAID:
57
ICTUS Study: International Citicoline Trial on acUte Stroke. A multicenter, prospective, randomized, double-blind, placebo-controlled study (Update at 3rd May 2010)
Background: Citicoline is a safe drug approved in some countries for the treatment of acute ischemic stroke. The drug has shown some evidence of efficacy in a data pooled analysis, based on four clinical trials performed in USA with oral citicoline given within 24 hours from symptoms onset.
Purpose: Confirm the results of the data pooled analysis.
Design: Multicenter, randomized (under minimization), double-blind, placebo-controlled trial, based on a sequential analysis (triangular model).
Sample Size: The study will follow a sequential analysis, with the first approach to test the efficacy with 1000 patients. The upper limit has been established in 2600 patients. This design has 80% power to establish a treatment effect of 1.26 (common odds ratio).
Active Centers: 29 centers in Spain, 10 in Portugal and 11 in Germany
Study Population: Male or female, >18 years old, treated within 24 hours of symptoms onset, with a measurable focal neurological deficit lasting for a minimum of 60 minutes. Baseline NIHSS score ≥ 8, with a neuroimage compatible with the diagnosis of acute ischemic stroke and symptoms referable to MCA territory. Pre-stroke mRS 0-1.
Interventions: Patients will be randomized in a 1:1 ratio to receive either citicoline or placebo. Citicoline forms: 1000 mg ampoules (4 cc) and 500 mg tablets. Daily dosage: 1000 mg/12 h i.v. during the first three days and orally from the fourth day until the end of the 6 weeks treatment period.
Outcome Endpoints: Primary end-point will consist in a global score test combining three measures of success evaluated 12 weeks after treatment on the basis of intention-to-treat criteria: neurological (NIHSS) 0-1), disability (MRS 0-1), and activities of daily life (BI 95-100), averaged using a Global Test.
Trial Status: 1497 patients included in the study by 3rd May 2010.
Graphic:
Table:
60 centres involved in the study
A.Davalos, Hospital Germans Trias i Pujol, Badalona, SPAIN
J.Alvarez-Sabin
Hospitals de la Vall d'Hebron
Barcelona
SPAIN
J.Castillo
Centro Hospitalario Universitario
Santiago de Compostela
SPAIN
E.Cobo
Universitat Politecnica de Catalunya
Barcelona
SPAIN
E.Diez-Tejedor
Hospital La Paz
Madrid
SPAIN
J.Ferro
Hospital Santa Maria
Lisboa
PORTUGAL
E.Martínez-Vila
Clinica Universitaria der Navarra
Pamplona
SPAIN
J.J.Secades
Ferrer Grupo
Barcelona
SPAIN
Ongoing Trials ESC Barcelona 2010
OAID:
58
EMG TRIGGERED ELECTRICAL STIMULATION IN ACUTE STROKE
Introduction:
In Australia each year, 48 000 people have a stroke and of this number about one third will be referred to rehabilitation. The primary impairment contributing to loss of function in stroke patients undergoing rehabilitation is loss of strength. The main objective of this randomised controlled trial is to determine whether EMG-triggered electrical stimulation applied to four muscle groups of the affected arm is more effective at increasing (i) strength and (ii) activity, than current physiotherapy intervention for very weak stroke patients.
Methods:
A prospective, randomised controlled trial of inpatient intervention with a 3 month follow-up with blinded assessment will be conducted. 70 stroke patients who are very weak i.e. less than grade three in three out of the four target arm muscles early after stroke will be recruited and randomly allocated to a control group or an experimental group. The control group will undertake usual therapy only while the experimental group will undertake usual therapy plus EMG triggered electrical stimulation to four muscles of the affected arm. The muscle strength of the target muscles of the affected arm and the activity of the affected arm will be measured.
Results:
Over 300 patients have been screened for eligibility. Of twenty three patients who were eligible one declined to participate. The other 22 participants were randomised, eleven to the experimental group and eleven to the control group. The mean age is 65.9 years (SD 12.8) and the mean time since stroke was 15.4 days (SD 6.3). The participants in the experimental group have received 82% of the experimental intervention and there have been no adverse events.
Discussion:
The results of this study will clearly identify effective intervention to establish better arm function after a stroke, thereby promoting an increase in independent living and community participation in the longer term.
Graphic:
Table:
Simone Dorsch, Louise Ada, Colleen Canning
S.Dorsch, University of Sydney, Sydney, AUSTRALIA
L.Ada
University of Sydney
Sydney
AUSTRALIA
C.Canning
University of Sydney
Sydney
AUSTRALIA
Ongoing Trials ESC Barcelona 2010
OAID:
59
Risk Awareness and Knowledge of Stroke: A Questionnaire Employed in a 3-D Environment.
The Potential of the Web-based Virtual World of Second Life (SL) in Stroke Research.
Background: Knowledge of stroke remains the mainstay in stroke prevention. Health care agencies increasingly choose SL, an online virtual reality world with over one million active users, as one of their Web 2.0 communication strategies. Objective: To provide insight into stroke risk awareness, knowledge and perception of stroke on an international level through the responses of SL users. Methods: A standard interviewer-assisted questionnaire was provided to randomly selected SL users. Socio-demographic factors including age, sex, ethnicity, educational level, nationality and personal history of stroke risk factors were assessed. Results: As of April 2010, 2,324 SL users (45% male, 42% aged >34 years, 72% Caucasian) from 116 countries worldwide responded to the questionnaire. Personal risk factors and lifestyle conditions were: smoking (25%), unhealthy food (20%), no sport (15%), hypertension (13%), high cholesterol (6%), heart disease (6%), diabetes (5%), stroke history (1%). Percentage of respondents who identified the given factors as stroke risk factors were: 69% hypertension, 63% smoking, 49% high cholesterol, 40% stress, 38% obesity, 31% alcohol consumption, 30% unhealthy food, 26% diabetes, 24% heart disease and 24% no sport. Symptoms identified as warning signs of stroke were: numbness/paralysis (60%, 58%), speech disorder (59%), dizziness (38%) and loss of vision (37%). 44% stated that stroke could happen to them at the time of interview, 73% would call the emergency number in case of stroke symptoms; both answers were given significantly (p=0.001) more often by persons aged >34 years and living in the US (versus Europe). Conclusions: Results of this ongoing international survey emphasize the potential of a 3-D virtual environment as a unique design feature in health-related activities and document that stroke awareness is suboptimal. These data support the need for targeted educational programs and improvement of the impact of real-life health-related behaviors.
Graphic:
Table:
Horner S, Niederkorn K, Jantet A, Fazekas F
S.Horner, Medical University of Graz, Department of Neurology, Graz, AUSTRIA
K.Niederkorn
Medical University of Graz, Department of Neurology
Graz
AUSTRIA
A.Jantet
Vitameo Conseil
Strasbourg
FRANCE
F.Fazekas
Medical University of Graz, Department of Neurology
Graz
AUSTRIA
Ongoing Trials ESC Barcelona 2010
OAID:
60
MR CLEAN, a multicenter randomized clinical trial of endovascular treatment for acute ischemic stroke in The Netherlands.
Background and purpose
Endovascular treatment increases the likelihood of recanalization in patients with acute ischemic stroke caused by proximal intracranial arterial occlusion. The purpose of MR CLEAN is to assess the safety and effect on functional outcome of endovascular treatment in these patients.
Methods
MR CLEAN is a pragmatic phase III multicenter randomized clinical trial with blind outcome assessment. We compare intra-arterial thrombolysis, mechanical thrombectomy or both, with no treatment, against a background of optimal medical management (including intravenous thrombolysis). The exact choice of endovascular treatment modality is left to the discretion of the local investigator. Patients should have a clinical diagnosis of acute ischemic stroke, confirmed by CT, an NIHSS score of 2 points or more, a relevant intracranial arterial occlusion on CTA, MRA or TCD and the possibility to start endovascular treatment within 6 hours.
Randomization will be stratified for center, treatment with intravenous alteplase, planned treatment modality and stroke severity according to the NIHSS. We will estimate the effect of treatment by means of ordinal logistic regression, which considers the whole range of the mRS. In total, 500 patients will be included. Assuming a 10% increase in the cumulative proportion of patients with mRS 0-3, this provides a power of 82% at a significance level of 0.05, taking into account a 10% cross over rate.
Outcome measures
The primary outcome is the score on the modified Rankin scale at 3 months. Secondary outcomes are NIHSS score and vessel patency at 24 hours, infarct size at day 5 and the occurrence of major bleeding.
Trial organization
Over 10 centers in the Netherlands will participate. The steering committee will issue recommendations and guidelines for treatment and selection of patients. Patient inclusion will take 4 years, and starts in May 2010. The trial is funded by The Netherlands Heart Foundation.
Graphic:
Table:
on behalf of the MR CLEAN investigators
P.S.SFransen, Erasmus MC University medical center Rotterdam, Rotterdam, THE NETHERLANDS
C.Majoie
AMC Amsterdam
Amsterdam
THE NETHERLANDS
A.van der Lugt
Erasmus MC University medical center Rotterdam
Rotterdam
THE NETHERLANDS
W.van Zwam
University Hospital Maastricht
Maastricht
THE NETHERLANDS
R.van Oostenbrugge
University Hospital Maastricht
Maastricht
THE NETHERLANDS
Y.Roos
AMC Amsterdam
Amsterdam
THE NETHERLANDS
DDippel
Erasmus MC University medical center Rotterdam
Rotterdam
THE NETHERLANDS
Ongoing Trials ESC Barcelona 2010
OAID:
61
The Asymptomatic Carotid Surgery Trial-2.
A large, simple randomised trial to compare carotid artery stenting versus carotid endarterectomy to prevent stroke
If a patient needs a procedural intervention for asymptomatic carotid stenosis, there may be substantial uncertainty whether to opt for carotid endarterectomy (CEA) or carotid artery stenting (CAS). By randomising such individuals between CEA & CAS, ACST-2 will compare both the immediate hazards of the two procedures when done by experienced doctors, and the subsequent stroke rates over the next 5 to 10 years. Like ACST-1 (1993-2003) a trial of CEA versus no immediate procedure (showing CEA could be effective) involving over 3000 patients, ACST-2 workload per patient is minimised.
Eligibility: Patients with asymptomatic carotid stenosis & thought to need some procedural intervention;angiography shows CEA and CAS are both anatomically practicable; both doctor and patient are substantially uncertain whether CEA or CAS is preferable.
Information & Consent: If a patient might well be eligible, then mention the study & give the information leaflet for consideration.
Randomisation: After consent is signed, complete at least the first half of the 1-page randomisation form before calling the 24-hour randomisation number +44 (0) 18 85 76 56 15 to obtain the treatment allocation (CEA or CAS) and the 6-digit patient id. This call takes about 2 minutes. Plan the allocated procedure to be done soon.
Treatment and 1-month post-procedural follow-up: Allocated procedures must be done by collaborators whose Track Record for that procedure has been approved. Review the patient 1 month afterwards and complete a short form to describe carotid patency and any peri- or post-procedural events.
Long-term follow-up: Annual follow-up for at least 5 years (to monitor any strokes) will be by the ACST office writing to the patient. After the 1-month post-procedural form, no further follow-up by the doctor is required (unless further details of a stroke need to be provided)
As the study is so easy, many hundreds of doctors and many thousands of patients can take part, and uniquely reliable evidence will then emerge comparing the immediate and the long-term safety of CEA and CAS.
The protocol is available on www.acst.org.uk
Graphic:
Table:
The ACST Collaborators
A.Halliday, St George's University of London, London, UNITED KINGDOM
S.MacDonald
Freeman Hospital
Newcastle
UNITED KINGDOM
E.Hayter
St George's University of London
London
UNITED KINGDOM
L.Hirt
Clinicla Trial Service Unit
Oxford
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
62
Bridges self management for stroke survivors in the community: an ongoing feasibility RCT
Background: There is only limited evidence for pyschosocial interventions specific to stroke survivors (Jones 2006). The Bridges programme consists of using a self-directed but professionally supported workbook to enhance self efficacy in order to improve patients’ self management skills (Jones et al, 2009). This ongoing RCT explores the feasibility of the Bridges stroke self management programme in a community setting. Methods: Stroke survivors within 4 weeks post stroke, are randomly allocated to either a BSMP or a control group. The BSMP is delivered alongside usual MDT care for six weeks by the CST. Participants are assessed by a blinded assessor at baseline, post intervention and 3 months post intervention. Primary outcomes are health related quality of life and self efficacy. Focus groups and exit interviews probe for further information relating to feasibility of delivery and user acceptability. Results: 24 participants have been recruited over a 15 month period (36% of all CST referrals). The main reason for exclusion from the trial is the need for less than 6 weeks CST rehabilitation (32%). Feedback from exit interviews with the participants enrolled in the BSMP has been unanimously positive. Conclusion: Recruitment targets are being met. This trial will demonstrate that it is feasible to deliver an individualised stroke self-management programme alongside usual MDT rehabilitation in stroke survivors. Results will inform the sample size and design of the next stage of research. Results will be available in August 2010.
References:
Jones F (2006) Strategies to enhance chronic disease self-management: how can we apply this to stroke? Disability & Rehabilitation 28: 13-14; 841-847.
Jones F, Mandy A, Partridge C (2009) Changing self-efficacy in patients following a first time stroke: preliminary study of a novel self-management intervention. Clinical Rehabilitation 23: 522-633.
Funded by Northern Ireland Chest, Heart & Stroke OREC no: 08/NIR01/67
Graphic:
Table:
Gillespie, Lennon, McKenna, Glenfield, Jones
S.Lennon, Centre for Rehabilitation Research, University of Ulster, Newtownabbey, UNITED KINGDOM
S.Gillespie
Centre for Rehabilitation Research, University of Ulster
Newtownabbey
UNITED KINGDOM
S.McKenna
Centre for Rehabilitation Research, University of Ulster
Newtownabbey
UNITED KINGDOM
P.Glenfield
Community Stroke Team, Southeastern Health & Social Care Trust
Belfast
UNITED KINGDOM
J.Crosbie
Centre for Rehabilitation Research, University of Ulster
Newtownabbey
UNITED KINGDOM
F.Jones
Faculty of Health and Social Care Sciences, St George’s University
London
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
63
The Field Administration of Stroke Therapy - Magnesium (FAST-MAG) Clinical Trial
The FAST-MAG Phase 3 Clinical Trial is an NIH-NINDS-sponsored study whose goal is to evaluate the effectiveness and safety of field-initiated magnesium sulfate in improving the long-term functional outcome of patients with acute stroke. This study will analyze magnesium sulfate versus placebo among 1700 ambulance-transported patients with acute stroke with study agent initiated within 2 hours of symptom onset. Paramedics initiate a loading dose of 4 grams magnesium sulfate iv over 15 minutes or matched placebo, followed after hospital arrival by a maintenance infusion of 16 grams magnesium sulfate iv over 24 hours or matched placebo. Follow-up assessments are performed at ED arrival, 24 hours, 48 hours, day 4, day 30, and day 90. The primary outcome is functional outcome 90 days after treatment. This trial will also demonstrate that paramedics can safely, effectively, and rapidly start neuroprotective therapies for stroke.
FAST-MAG is currently underway in Los Angeles County, California with plans to expand the study to Orange County, California. There are currently 996 subjects enrolled and over 1000 are expected by the end of May. As of the latest data assessment point the median symptom onset to treatment time is 44 minutes and approximately 1 in 4 has intracerebral hemorrhage.
FAST-MAG is the first prehospital stroke treatment trial and the first “golden hour” (<1 hr) stroke treatment trial. Other FAST-MAG innovations include the first acute (<3 hr) neuroprotective stroke treatment trial, the first trial of neuroprotective drugs before recanalization therapies, and the first prehospital randomized clinical trial for any condition employing physician-elicited informed consent.
Graphic:
Table:
FAST-MAG Investigators and Nurses
N.Sanossian, University of Southern California, Los Angeles, USA
J.L.Saver
University of California Los Angeles
Los Angeles
USA
S.Starkman
University of California Los Angeles
Los Angeles
USA
S.Stratton
University of California Los Angeles
Los Angeles
USA
M.Eckstein
University of Southern California
Los Angeles
USA
F.Pratt
Los Angeles County Fire Department
Los Angeles
USA
S.Hamilton
Stanford University
Palo Alto
USA
R.Conwit
National Institutes of Health
Bethesda
USA
D.S.Liebeskind
University of California Los Angeles
Los Angeles
USA
C.S.Kidwell
Georgetown University
Washington D.C.
USA
G.Sung
Univeristy of Southern California
Los Angeles
USA
Ongoing Trials ESC Barcelona 2010
OAID:
65
The International Carotid Stenting Study ICSS: Patient preferences and long-term outcomes.
Background: The International Carotid Stenting Study (ICSS) having recruited 1710 patients, reported that the 30-day rate of stroke or death after carotid artery stenting (CAS) was significantly higher at 7.4% compared with 3.4% after carotid endarterectomy (CEA). However, only 1 in 25 patients would have an additional event by choosing CAS over CEA. Preliminary work suggests patients given the figures may still opt for CAS if they have a preference for avoiding surgery. In addition to completing long term clinical follow to compare treatment durability and efficacy, we will study what determines patient and clinician preferences given different treatment outcomes.
Methods: The International Carotid Stenting Study (ICSS), a follow-on study to CAVATAS, is an international, multicentre, randomised, controlled, open, prospective clinical trial comparing stenting with endarterectomy for symptomatic carotid artery stenosis. Patients over 40 years of age with atherosclerotic carotid stenosis, suitable for both stenting and surgery were randomised to carotid endarterectomy or stenting. Annual patient follow up by neurologists at participating centres with Doppler ultrasound to assess restenosis and rates of recurrent stroke is continuing. The primary outcome measure is long term survival free of fatal or disabling stroke. We will also survey selected ICSS patients and clinicians, eliciting their perceptions and preferences between stenting and endarterectomy given the establised risks and benefits using survey methods, including a Discrete Choice Experiment (DCE).
Progress: 1710 patients were recruited into ICSS and safety data announced in 2009. Long-term follow up will continue until 2011. Recruitment of patients for the preference study is commencing. Further details may be found at www.cavatas.com
Funding: The trial is funded by grants from the UK Medical Research Council and The Stroke Association.
Graphic:
Table:
The ICSS Investigators
R.L.Featherstone, UCL Institute of Neurology, London, UNITED KINGDOM
D.Doig
UCL Institute of Neurology
London
UNITED KINGDOM
M.M.Brown
UCL Institute of Neurolgy
London
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
66
The International PFO Consortium: Secondary Stroke Prevention In Patients With Patent Foramen Ovale
The International PFO Consortium is an informal academic collaboration of researchers from Europe and North America. The Consortium collects and analyzes data on patients with patent foramen ovale (PFO) and ischemic stroke or transient ischemic attack (TIA). It reflects the joint commitment of neurologists and cardiologists to study the secondary stroke prevention in a large cohort of patients with PFO. Emphasis is placed on the evaluation of risk factors, diagnostics, and treatment with antithrombotic drugs (ATT) and percutaneous device closure (PDC).
Aims:
1. Comparison between ATT and PDC for secondary stroke prevention in patients with PFO. 2. Identification of "high risk" patients with either treatment.
Methodology:
Multicenter prospective non-randomized study with scheduled 3-years follow-up of patients with PFO and ischemic stroke or TIA.
Inclusion criteria:
1. Men and women older than 18 years with ischemic stroke or TIA within the previous 3 months. 2. Diagnosis of PFO established by transesophageal echocardiography (TEE).
Primary endpoints:
1. The cumulative risk of recurrent stroke and that of recurrent stroke and TIA at 3 years of follow-up. 2. Average annual event rates in both the ATT and the PDC group will be calculated according to the formula 1 – (1 – P)n, where P equals the cumulative event rate at n years of follow-up.
Results:
As of May 13, 2010, 286 patients (39% women) with PFO and ischemic stroke or TIA have been included. Nine patients have been enrolled since last month. The mean age is 54 years. One hundred and twenty-four patients (43%) have undergone PDC, the remaining 162 receive ATT. Follow-up data are collected every 12 months using a standardized questionnaire.
Outlook: The International PFO Consortium is calling stroke researchers who are interested in pooling their efforts in the field of PFO-related disorders to join the Consortium.
ClinicalTrials.gov Identifier: NCT00859885
Graphic:
Table:
KNedeltchev, Dept. of Neurology, Triemli Hospital Zurich and University of Bern, Zurich, SWITZERLAND
M.L.Mono
Dept of Neurology, Inselspital, University of Bern
Bern
SWITZERLAND
M.Zbinden
Department of Neuroradiology, Inselspital, University of Bern
Bern
SWITZERLAND
D.E.Thaler
The Comprehensive Stroke Center at Tufts Medical Center
Boston
USA
M.Arnold
Dept. of Neurology, University of Bern
Bern
SWITZERLAND
P.Michel
Dept. of Neurology, CHUV Lausanne
Lausanne
SWITZERLAND
S.Engelter
Dept of Neurology, University Hospital of Basel
Basel
SWITZERLAND
L.Collins
East Texas Medical Center
Tyler
USA
F.Eberli
Dept. of Cardiology, Triemli Hospital
Zurich
SWITZERLAND
A.Luft
Dept. of Neurology, University Hospital of Zurich
Zurich
SWITZERLAND
C.Weimar
Dept. of Neurology, University of Duisburg-Essen
Essen
GERMANY
H.U.Sorgenfrei
Dept. of Neurology, Alfried Krupp Hospital
Essen
GERMANY
R.Diehl
Dept. of Neurology, Alfried Krupp Hospital
Essen
GERMANY
H.P.Mattle
Dept. of Neurology, Inselspital, University of Bern
Bern
SWITZERLAND
B.Meier
Dept. of Cardiology, Inselspital, University of Bern
Bern
SWITZERLAND
Ongoing Trials ESC Barcelona 2010
OAID:
67
The Second European Carotid Surgery Trial (ECST-2): Pilot study
Background: The European Carotid Surgery Trial (ECST) and other randomized controlled trials established the benefit of carotid endarterectomy (CEA) for moderate to severe carotid stenosis. However, a risk model derived from ECST showed that only patients with a high risk of stroke on medical therapy benefit from CEA. For many patients there is neither clear benefit nor harm from CEA. Medical therapy for prevention of stroke in patients with carotid disease has improved considerably since these original trials were concluded, with more widespread use of statins, more active lowering of blood pressure and more effective antiplatelet agents. Therefore optimized medical therapy (OMT) using up-to-date regimes may obviate the need for CEA in many patients with symptomatic carotid disease. We therefore designed ECST-2 to address the question: is OMT alone equally efficient in the long-term prevention of stroke compared with CEA and OMT combined in patients at low and intermediate risk for stroke?
Methods: ECST-2 is an international, multicentre, randomised, controlled, open, prospective clinical trial. Patients with carotid stenosis (> 50% by NASCET criteria) suitable for CEA either asymptomatic or symptomatic with a low or intermediate Carotid Artery Risk (CAR) score will be randomized between OMT alone or CEA and OMT combined. OMT will include adjustment to achieve target blood pressure and cholesterol levels. The CAR score will estimate the 5 year ipsilateral stroke risk of patients based on their demographic characteristics. The trial has the primary outcome of long term survival free of any stroke or perioperative death and secondary outcome measures including myocardial infarction, disabling stroke or hospitalisation for vascular disease during follow up, quality of life and economic measures.
Progress: We are currently recruiting centres and will commence randomization in 2010.
Funding: The trial is funded by a grant from the UK National Institute for Health Research.
Graphic:
Table:
The ECST-2 Investigators
R.L.Featherstone, UCL Institute of Neurology, London, UNITED KINGDOM
D.Doig
UCL Institute of Neurology
London
UNITED KINGDOM
M.M.Brown
UCL Institute of Neurology
London
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
68
COOL-AID OERESUND
A Multicenter Pilot Study of Cooling in Ischemic Stroke
Part of EURO-HYP
Background:
Stroke is one of the most common and costly causes of death and disability. Evidence based treatment comprizes specialized stroke unit (SU) care and acute thrombolytic treatment. However, many stroke patients sustain severe neurologic deficits with deleterious impact on quality of life.
Animal experiments indicate that hypothermia is an effective neuroprotective treatment for ischemic stroke. Mild hypothermia is used to protect the brain of cardiac arrest victims. The patient is actively cooled to 33ºC for 24 hours. Cooling has so far been tried in stroke-patients in a few and relatively small studies, mainly including patients with high NIHSS and large infarctions.
Study design:
Feasibility and safety of a cooling regimen compared to standard SU management in patients with ischaemic stroke measured at 30 d after stroke wit assessment of SAE and mortality. Multicenter Randomized Controlled Trial with stratification for iv rTPA. Total patient number 2x20.
Main inclusion criteria:
Patients with acute ischemic stroke with NIHSS 4-18, who do not improve significantly after 3 hours of SU-treatment, including iv rTPA if warranted.
Main exclusion criteria:
Pulmonary disease or other significant medical conditions including pre-stroke mRS >2.
Treatment:
Cooling on an ICU to 33ºC for 24 hours according to standard protocol used for cardiac arrest victims with controlled rewarming rate of 0.5 ºC/h.
Recruitment status:
20 patients
Study Centers:
Department of Neurology and Anestesiology, Malmö, Lund University
Departement o Neurology and Anestesiology, Bispebjerg, Copenhagen University
Department of Neurology, Halle, Martin Luther University
Contact: jesper.petersson@skane.se
Graphic:
Table:
J.Petersson, Neurology, Malmö, Lund University, Malmoe, SWEDEN
M.Brizzi
Neurology, Malmö, Lund University
Malmoe
SWEDEN
A.Ersson
Anestesiology, Malmö, Lund University
Malmoe
SWEDEN
T.Karlsson
Anestesiology, Malmö, Lund University
Malmoe
SWEDEN
K.Wartenberg
Neurocritical Care, Martin Luther University
Halle
GERMANY
H.Christensen
Neurology, Bispebjerg University Hospital
Copenhagen
DENMARK
F.Pott
Anestesiology, Bispebjerg University Hospital
Copenhagen
DENMARK
D.Krieger
Neurology, Bispebjerg University Hospital
Copenhagen
DENMARK
Ongoing Trials ESC Barcelona 2010
OAID:
69
The Stroke Oxygen Supplementation (SOS) Study
Background
Hypoxia after stroke is common, often missed, has significant adverse effects on the ischaemic brain, and is associated with worse outcome. Oxygen supplementation could prevent hypoxia and related brain damage and lead to better recovery from the stroke. However, there is some evidence from preclinical studies that hyperoxia may be neurotoxic, and a small clinical study of short-term fixed dose oxygen supplementation did not show overall benefit. Oxygen supplementation may interfere with mobilization and thus affect early rehabilitation. Since hypoxia is most likely to occur at night, restricting routine supplementation to night time may be better than continuous oxygen or no routine oxygen. Current guidelines on oxygen supplementation are not based on evidence from clinical trials and differ between countries and organizations.
Aims
1. To determine if patients benefit from routine oxygen supplementation after stroke
2. To establish whether nocturnal oxygen supplementation is as effective as, or more effective than, continuous oxygen supplementation.
Inclusion criteria
Patients with a clinical diagnosis of acute stroke who have no clear indication for and no clear contraindication against oxygen treatment are recruited within 24 h of hospital admission.
Intervention
1. No routine oxygen supplementation during the first 72 hours after randomisation
2. Oxygen per nasal cannula over night at a rate of 3L/min (if baseline oxygen saturation is 93% or below) or of 2L/min (if baseline oxygen saturation is >93%)
3. Oxygen (delivered and dosed as in 2) continuously (day and night) for 72 h
Assessments
1 week by the local investigator (clinical examination, complications, compliance and NIHSS) 3, 6, and 12 months via postal questionnaire sent out by the trial centre (modified Rankin (mRS), Barthel Index, EuroQuol, Nottingham EADL).
Study size: 6600 subjects
Progress (1.5.10): 65 centres open, 1369 patients recruited.
Trial website: www.so2s.co.uk
Graphic:
Table:
C Roffe et al on behalf of the SOS collaborators
C.Roffe, North Staffordshire Combined Healthcare NHS Trust, Stoke-on-Trent, UNITED KINGDOM
S.Pountain
North Staffordshire Combined Healthcare NHS Trust
Stoke-on-Trent
UNITED KINGDOM
P.Crome
North Staffordshire Combined Healthcare NHS Trust
Stoke-on-Trent
UNITED KINGDOM
R.Gray
Birmingham University Clinical Trials Unit
Birmingham
UNITED KINGDOM
P.Jones
Keele University
Stoke-on-Trent
UNITED KINGDOM
L .Handy
Stroke R Us
Stoke-on-Trent
UNITED KINGDOM
P.Handy
Stroke R Us
Stoke-on-Trent
UNITED KINGDOM
Ongoing Trials ESC Barcelona 2010
OAID:
70
ARUBA - A Randomized trial of Unruptured Brain AVMs
RATIONALE: Current invasive treatment for brain arteriovenous malformations (AVMs) is highly specialized and includes endovascular procedures, neurosurgery, and radiotherapy alone and in combination. Carefully planned intervention generally leads to successful AVM eradication with relatively low treatment-related morbidity and mortality.
The goal of this randomized controlled trial is to compare the long-term outcomes of patients who receive medical management for symptoms (e.g., headache, seizures) associated with an unruptured AVM to those who receive medical management and invasive therapy to eradicate the brain AVM.
DESIGN: ARUBA is an international, multicenter, randomized, controlled, open, prospective clinical trial.
SAMPLE SIZE: 400 patients (1:1 random assignment).
POPULATION STUDIED: Patients aged ≥18 years, diagnosed with an unruptured brain AVM considered treatable by the local investigators.
INTERVENTIONS: Patients will be randomly assigned to invasive therapy (AVM cure by means of endovascular, surgical, and/or radiation therapy) versus medical management alone. The study protocol will not modify any routine treatment strategies in either arm. Patients will be followed for a minimum of 5 years and a maximum of 10 years from randomization.
OUTCOME MEASURES: The primary outcome measure is the composite endpoint of death from any cause or stroke (clinically symptomatic hemorrhage or infarction confirmed by imaging). The secondary outcome measure is long-term clinical status by Rankin Scale, NIHSS, SF-36, and EuroQol.
TRIAL STATUS: N=121 patients have been enrolled with a current recruitment rate of 1-2 patients per week. Participating sites currently include multidisciplinary treatment centers in the US, Australia, Austria, Brazil, Canada, Finland, France, Germany, Italy, Netherlands, Spain, Switzerland, and the UK.
REGISTERED: http://clinicaltrials.gov/ct2/show/NCT00389181
SPONSOR: NIH/NINDS
FUNDING: US-$ 4,500 (+8% institutional overhead) for each case randomized and followed over 5 years.
CONTACT: christian.stapf@lrb.aphp.fr (Paris), jpm10@columbia.edu (New York)
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for the international ARUBA Collaborators
C.Stapf, Dept. of Neurology, Hôpital LAriboisière, Paris, FRANCE
A.J.Moskowitz
InCHOIR, Mount Sinai School of Medicine
New York
USA
M.K.Parides
InCHOIR, Mount Sinai School of Medicine
New York
USA
C.S.Moy
NIH/NINDS
Bethesda
USA
E.Vicaut
Clinical Research Unit (U.R.C.), Hôpital Lariboisière
Paris
FRANCE
J.P.Mohr
Columbia UNiversity Medical Center
New York
USA
Ongoing Trials ESC Barcelona 2010
OAID:
71
MAGIC study: Biological markers in acute ischemic stroke. Ongoing national multicentric observational study
Background: Functional outcome after ischemic stroke can vary on the basis of a number of co-factors including pathophysiology, extent of the ischemic lesion, and comorbidities. Thrombolytic treatment and stroke unit admission can improve outcome in over one third of patients. Preliminary observational data suggest that some biomarkers detected in the acute phase of ischemic stroke can predict functional outcome and incidence of complication Objective: to evaluate the role of biomarkers as predictors of hemorrhagic transformation and functional outcome after thrombolysis, and to explore their usefulness in the clinical setting, in combination with other validated clinical and radiological markers, for the most appropriate selection of candidates to acute treatment strategies. Methods: MAGIC is an observational multicentric study. Consecutive patients (18-80 years old) with acute ischemic stroke, fitting the SITS-MOST criteria, are currently being enrolled in several Centres across Italy. Considering metalloproteinase-9 as biomarker of reference and a statistical power of 0.80 (alfa error 0.05) with a relative risk of 2.00, we estimated a sample size of 400 patients, assuming a positive effect of thrombolysis in 50% of patients. Blood samples for endopeptidase and their inhibitors, hemostasis, inflammation and immunomodulation markers are drawn at baseline, 24 hours, and 3 months and centrally analysed, together with clinical, functional and neuroimaging data. Primary outcome is disability at 3 months (as measured using the modified Rankin scale < or >2). Secondary Outcome Measures are neurological score (NIHSS < or ≥ 8 at 48 h), ), symptomatic haemorrhage, extension of the ischemic lesion (using the ASPECT Score at baseline and 24 hours). As of May 12th, 147 patients have been enrolled. Results are expected by the end of 2012
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MAGIC Investigators
BPiccardi, Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ITALY
VPalumbo
Department of Neurological and Psychiatric Sciences, University of Florence
Florence
ITALY
MNesi
Department of Neurological and Psychiatric Sciences, University of Florence
Florence
ITALY
P.Nencini
Department of Neurological and Psychiatric Sciences, University of Florence
Florence
ITALY
G.Pracucci
Department of Neurological and Psychiatric Sciences, University of Florence
Florence
ITALY
B.Giusti
Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence
Florence
ITALY
A.M.Gori
Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence
Florence
ITALY
R.Abbate
Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence
Florence
ITALY
D.Inzitari
Department of Neurological and Psychiatric Sciences, University of Florence
Florence
ITALY
Ongoing Trials ESC Barcelona 2010
OAID:
75
THE URICO-ICTUS STUDY. A phase 3 study of Combined Treatment With Uric Acid and rtPA in Acute Ischemic Stroke Patients Within the First 4.5 Hours of Symptoms Onset.
Background: Oxidative stress is a major contributor to brain damage in patients with ischemic stroke. Uric acid (UA) is a potent endogenous antioxidant molecule. In experimental ischemia in rats, the exogenous administration of UA is neuroprotective and enhances the effect of rt-PA. Moreover, in acute stroke patients receiving rtPA within 3 hours of stroke onset the intravenous administration of UA is safe, prevents an early fall in UA levels and reduces an early increase in oxidative stress markers and in matrix degrading enzymes (MMP9) levels.
Purpose of the study: To determine whether the combined treatment with UA and rtPA is superior to rtPA alone in terms of clinical efficacy in acute ischemic stroke patients treated within the first 4.5 hours of symptoms onset.
Study design: Multicenter, interventional, randomized, double blind, vehicle controlled, efficacy study with parallel assignment (1:1).
Estimated enrollment: 420 patients over 3 years, starting in September 2009.
Treatment arms: Included patients will receive a single intravenous infusion of 1 gram of UA dissolved in a vehicle (500 ml of 0'1% Lithium Carbonate and 5% Mannitol) (n=210), or vehicle alone (n=210).
Inclusion and exclusion criteria: The study will include patients older than 18 years old, treated with rtPA within the first 4.5 hours of clinical onset and with a baseline NIHSS>=6 and <25 and a mRS score <=2 prior to the ischemic event. Patients with renal insufficiency, gout or asymptomatic hiperuricemia treated with allopurinol will be excluded.
Outcome measures: The primary outcome measure is the proportion of patients achieving a mRS of 0 to 1 at 3 months after treatment, or 2 in those patients with a prior qualifying mRS of 2. Secondary outcome measures include final infarction volume measured at 72 hours and the proportion of patients with symptomatic intracranial hemorrhage (≥4 points increase in NIHSS score).
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URICO-ICTUS trialists
S.Amaro, Hospital Clinic, Barcelona, SPAIN
J.Martí-Fabregas
Hospital de la Santa Creu i Sant Pau
Barcelona
SPAIN
M.Castellanos
Hospital Universitari Dr. Josep Trueta
Girona
SPAIN
J.Gállego
Hospital de Navarra
Pamplona
SPAIN
T.Segura
Hospital Gral. Universitario de Albacete
Albacete
SPAIN
D.Cánovas
Hospital de Sabadell
Sabadell
SPAIN
J.F.Arenillas
Hospital Clínico Universitario de Valladolid
Valladolid
SPAIN
A.Chamorro
Hospital Clínic
Barcelona
SPAIN
Ongoing Trials ESC Barcelona 2010
OAID:
76
A study of the visual processing in stroke patients using visual search tasks with local and global figures.
Background: Visuo-spatial and perceptual deficits are common in stroke patients, and result from the disruption of perceptual systems. The aim of this study is to evaluate the performance of stroke patients with a lesion in the right (STROKE-R) or in the left hemisphere (STROKE-L) in visual search tasks that require different levels of processing (global vs. local figures). Method: We generated a visual search task with 3 different targets: a local figure (consisting of a single element), a global figure (a kanizsa triangle) or a local figure combined with a global figure. 12 stroke patients and t10 controls participated in the experiment. In order to control for the complexity of the visual search task, this was presented with different number of distractors (6, 17 or 52). Subjects had to indicate by pressing the left or right button whether a target was present or not. Results: Lower accuracy and higher response time (RT) were found in patients compared to the control group (P < 0.005). There were no differences in accuracy between the STROKE-L and STROKE-R groups. However, the efficiency in the visual search task with the global figure was higher in the STROKE-L (103 ms/item) than in the STROKE-R group (174 ms/item). The STROKE-R participants required also more time than the other patients to find the local figure inserted in the global figure (p=0.01). Interestingly, stroke patients performed better the global task when it was preceded by the local task (p=0.023), contrary to the control group. Discussion: these first findings suggest, as other previous studies, the evidence of hemispheric asymmetry for processing global vs local levels of visual information. Our main objective is to complete the study and use the findings in order to design visuo-perceptual rehabilitation technology adapted to the patients needs. In the context of the RGS (Rehabilitation Gaming System) project, we aim at exploiting our findings in virtual reality tasks for the rehabilitation of stroke patients.
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C.Campillo, Universitat Pompeu Fabra - SPECS , Barcelona, SPAIN
S.Bermúdez-i-Badia
Universitat Pompeu Fabra - SPECS
Barcelona
SPAIN
S.Rodriguez
Hospital Vall d´Hebron
Barcelona
SPAIN
E.Duarte
Hospital de l´Esperança
Barcelona
SPAIN
P.F.M.J.Verschure
Universitat Pompeu Fabra - SPECS - ICREA
Barcelona
SPAIN