(For changes and additions to the trials,
please contact Rebecca Clarke, Managing Editor of Stroke, at rebecca.clarke{at}lhsc.on.ca.)
Aortic Arch Related Cerebral Hazard (ARCH)
This study is designed to compare the efficacy of warfarin
(target INR 2.0 to 3.0) with that of aspirin (75 to 150 mg per day) in
combination with clopidogrel (75 mg per day) in the
secondary prevention of vascular events in patients with stroke or systemic
arterial embolism who are found to have significant atheroma
of the aortic arch. Patients will be followed by 4 monthly reviews from
randomization to the end of the study. The primary end point is time to one of
a composite of recurrent ischemic stroke, intracranial hemorrhage, myocardial
infarction, peripheral embolism or vascular death.
Steering Committee: P. Amarenco, G.A.
Donnan, S.M. Davis, B.R. Chambers, A. Cohen, G.J. Hankey, E. Jones, C.R. Levi and P. Ravaud.
Contact: Australia: Prof Geoffrey Donnan,
Coordination Centre, NSRI, Level 1, Neurosciences Building, Austin Health, 300 Waterdale Road, Heidelberg Heights, Vic 3081, Australia. Phone 61 3 9496 2699. Fax 61 3 9457 2650.
E-mail: donnan@unimelb.edu.au. Europe: Prof Pierre Amarenco, Department of Neurology and Stroke Centre, Bichat
-
Location:
Number of Centers:
Sponsors: The National Health and Medical Research Council of
Dates of Study: Oct 2002 to Dec 2011
Asymptomatic Carotid Emboli Study (ACES)
Better ways are required to identify high risk patients with asymptomatic
carotid stenosis who may be suitable for endarterectomy. Previous small studies have suggested that
the presence of asymptomatic embolic signals detected using transcranial
Doppler ultrasound may identify a high risk group. ACES is a large multicentre international prospective study which will
determine whether asymptomatic emboli detected in the middle cerebral artery
are an independent predictor of stroke and TIA risk in patients with
asymptomatic carotid stenosis (≥ 70%). Carotid stenosis is identified by duplex ultrasound. Unilateral
middle cerebral artery transcranial Doppler
recordings are made for one hour on each of two occasions at study entry.
Recordings are made onto digital audiotape and are analysed
by the coordinating centre, blinded to subject identity. Subjects are then
followed for two years, at six monthly intervals with repeat 1 hour Doppler
recordings at 6, 12, and 18 months and repeat carotid duplex at 12 months.
There is also an option to perform cerebrovascular
reactivity measurements at study entry. Recruitment began in 2000. 482 patients
are enrolled in the study. Enrollment is now complete. Follow-up will be
completed in 2009.
Contact: Jennifer Siegel, ACES Study Coordinator, Centre for
Clinical Neuroscience, St. George's University London, SW17 ORE, Phone 020 8725
1369, Fax 020 8725 2950, E-mail acestrial@sgul.ac.uk
Location:Austria, China, Croatia,
France, Georgia, Germany, Hong-Kong, Ireland, Israel, Italy, Lithuania,
Netherlands, Poland, Singapore, Slovenia, Spain, United Kingdom (coordinating
center location), United States
Number of Centers: 29
Sponsor: British Heart Foundation
Dates of Study: 2000-2009
Asymptomatic Carotid Surgery Trial (ACST)
This is an international, multicenter trial to
assess the place of carotid endarterectomy (CEA) in
the management of patients with severe carotid stenosis
that are currently asymptomatic. Patients were randomized either to best
medical treatment (BMT) alone or to BMT plus CEA. Recruitment is now complete,
and 5-year results were published in The Lancet in May 2004, but follow-up
continues.
Principal Investigators: A.W. Halliday,
FRCS; A.O. Mansfield, FRCS; and D.J. Thomas, MD, FRCP
Contact: Steven Robertson, Trial Manager. Phone
+44(0) 20 8725-3746. Fax +44(0)20 8725-3782.
E-mail:acst@sgul.ac.uk
Location: The ACST Office, Department of Cardiac and Vascular
Sciences, St. Georges University of London, Cranmer Terrace,
Number of Centers: 120+
Sponsor: Stroke Association and Medical Research Council (UK)
Dates of Study: Commenced April 1993 (follow-up ongoing for
publication of 10-year results in 2007/2008, but recruitment closed in 2003)
Blood Pressure in Acute Stroke Collaboration (BASC)
Hypertension and hypotension in the acute phase of stroke are associated
with a poor outcome; paradoxically, lowering blood pressure may also worsen
outcome. BASC is performing a systematic review of blood pressure change versus
outcome in acute stroke trials that involve vasoactive
agents. Both group and individual patient data are being analyzed to assess
whether therapeutic alteration of blood pressure is safe and effective in
improving outcome, and if so, with which agent. Authors of such trials who are
willing to share their trial data are invited to contact the investigators.
Principal Investigator: Philip Bath, FRCP
Contact: P.M.W. Bath, FRCP; Division of Stroke Medicine,
Location:
Number of Centers: Those centers that have organized a
randomized controlled trial in acute stroke involving a vasoactive
drug which lowers or raises blood pressure.
Sponsor:
Dates of Study: November 1995 (continuing)
Carotid Occlusion Surgery Study (COSS)
COSS is a randomized, partially blinded, controlled trial to test whether extracranial-intracranial arterial bypass surgery, when
added to best medical therapy, can reduce by 40% subsequent ipsilateral
ischemic stroke at 2 years in subjects with recently symptomatic internal
carotid artery occlusion and ipsilateral increased
oxygen extraction fraction measured by PET. PET scans will be performed within
120 days of the qualifying TIA or stroke on 1400 clinically eligible subjects
to identify 372 with increased oxygen extraction fraction distal to an occluded
carotid who will be randomized to receive surgery or no surgery. Study
participants will be followed for a 2-year period. Follow-up includes clinic
visits at 1 month, and every 3 months after randomization for 2 years. All
participants will receive best medical management, which includes management of
hypertension and other medical risk factors.
Principal Investigators: William J. Powers, MD (Clinical
Coordinating Center), William R. Clarke, PhD (
Location: University of North Carolina, Chapel Hill, NC
(Clinical Coordinating Center) University of Iowa, Iowa City, IA (Data
Management Center)
Number of Centers: 40 to 50
Sponsor: National Institute of Neurological Disorders and
Stroke, National Institutes of Health
Dates of Study: July 2002--July 2013
Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)
CREST is a prospective, randomized, multicenter,
clinical trial to assess the relative efficacy of carotid endarterectomy
(CEA) versus carotid artery stenting (CAS) using the
RX ACCULINK Carotid Stent System and RX ACCUNET
Embolic Protection Device in preventing stroke, myocardial infarction and death
during the 30-day periprocedural period and ipsilateral stroke thereafter in subjects with symptomatic
and asymptomatic extracranial carotid stenosis. The study includes a lead-in phase for
credentialing of interventionalists, beyond their
initial training and certification requirements. Approximately 2500 subjects
with transient ischemic attack, amaurosis fugax, or nondisabling stroke
within 180 days of randomization and ipsilateral
carotid stenosis ≥ 50% for symptomatic patients
(defined as ≥ 70% by ultrasound, ≥ 50% by conventional angiography,
or ≥ 70% by CTA or MRA when ultrasound is 50% to 69%) and ≥ 60% for
asymptomatic patients (defined as ≥ 70% by ultrasound, ≥ 60% by
conventional angiography, or ≥ 80% by CTA or MRA when ultrasound is 50%
to 69%) will be enrolled and followed. Follow-up includes clinic visits at 1,
6, and 12 months, then every 6 months for study duration with phone contact
every 3 months. All patients will receive best medical management, which
includes treatment with aspirin, management of hypertension and medical risk
factors. Recruitment of patients began in December 2000 and ended July 18,
2008. In addition to 1561 Lead-In participants, target enrollment of 2500
randomized (53% symptomatic; 47% asymptomatic) has been achieved at 125
clinical centers in the
Principal Investigator: Thomas G. Brott,
MD
Contact: Alice Sheffet, PhD,
CREST-Administrative Center, UMDNJ-New Jersey Medical School, 30 Bergen Street,
ADMC 617, Newark, New Jersey 07017, USA. Phone 973-972-7718. Fax 973-972-8383.
E-mail: sheffeaj@umdnj.edu
Location:
Number of Centers: 125
Sponsor: National Institute of Neurological Disorders and
Stroke, National Institutes of Health; Abbott Vascular, Inc
Dates of Study: 2000 to 2011
CLOTS Trial (Clots in Legs or sTockings after Stroke): A randomized trial to establish the effectiveness of graduated compression stockings to prevent poststroke deep-vein thrombosis.
The CLOTS Trial is a family of 2 multicenter,
international, partially blinded, randomized controlled trials which aim to
establish the effectiveness of graduated compression stockings (GCS) to prevent
poststroke deep-vein thrombosis (DVT). Trial 1 is
comparing full-length GCS with no GCS, whilst Trial 2 is comparing full-length
and below-knee GCS. Centers randomize consenting patients into either Trial 1
or 2 depending on their current practice and beliefs with respect to GCS after
stroke. Patients who are admitted to hospital within 1 week of an acute stroke
and are immobile can be randomized into CLOTS. The allocated type of GCS is
applied to both legs as soon as possible after randomization and worn until the
patient is independently mobile around the ward or until they are discharged
from hospital or until the patient declines to wear them. Patients undergo a
routine Doppler ultrasound of both legs at 7, and wherever possible, 30 days postrandomization. The primary outcomes are the presence of
DVT in the popliteal vein or more proximal vein
detected on either Doppler ultrasound or venography
within 7 and 30 days of randomization. Patients are followed-up at 6 months to
identify late events, survival and functional status.
Chief Investigator: Professor Martin Dennis, Neurosciences
Trials Unit,
Location: Europe,
Number of Centers: 126 centers to date.
Sponsor: Medical Research Council (
Dates of Study: 2001—2009
The Continue Or Stop post-Stroke Antihypertensives Collaborative Study (COSSACS)
Summary: Up to 40% of acute stroke patients on hospital admission are
already taking antihypertensive therapy, and most will develop elevated blood
pressure levels as an acute complication of the stroke. However, no guidelines
exist as to whether antihypertensive therapy should be continued or
discontinued after acute stroke. The Continue Or Stop
post-Stroke Antihypertensives Collaborative Study
(COSSACS) is a multicenter, prospective, randomized,
open, blinded-end point study to assess whether existing antihypertensive
therapy should be continued or discontinued within 48 hours of stroke onset and
for the subsequent 2 weeks. A study population of 2900 patients with both
cerebral infarction and hemorrhage on antihypertensive treatment at hospital
admission will be recruited giving the study a 90% power at the 5% significance
level to detect a relative reduction of 10% (absolute risk reduction of 6%) in
death and dependency between continuation and discontinuation groups at 2
weeks. Nondysphagic, hospital-admitted stroke
patients will be recruited within 48 hours of stroke onset and also within 48
hours of last dose of pre-existing antihypertensive therapy. Baseline
investigations will include blood pressure measurement using UA-767 monitor,
modified Rankin Scale score, Barthel Index, National
Institutes of Health Stroke Score and Oxfordshire
Community Stroke Project Classification. Patients will be centrally randomized
by secure website to continue or discontinue pre-existing antihypertensive
treatment for a 2-week period. Blood pressure,
modified Rankin Scale score, Barthel Index and
National Institutes of Health Stroke Score will be repeated at 2 weeks by an
observer blinded to the randomized group. Mortality and health-related quality
of life outcomes will be centrally recorded at 6 months. The primary outcome
will be death or dependency (modified Rankin Scale score >3) at 2 weeks postrandomization. Early secondary outcomes of neurological
deterioration, functional status, blood pressure changes from admission and
discharge destination will be recorded at 2 weeks. Late secondary outcome
measures of death and dependency, fatal and nonfatal stroke recurrence,
functional status, health-related quality of life and discharge destination
will be recorded at 6 months.
Principal Investigators: Professor T.G. Robinson and Professor
J.F. Potter
Contact Details: Department of Cardiovascular Sciences,
Location:
Sponsor: The Health Foundation
Date of Study: December 2002 (ongoing)
Efficacy of Nitric Oxide in Stroke (ENOS) trial
Nitric oxide is a multimodal molecule, which is a candidate treatment for
acute ischemic and hemorrhagic stroke, as based on preclinical and clinical
data from 3 phase II trials. Potential mechanisms of action include lowering
blood pressure, improving cerebral perfusion, and neuroprotection.
ENOS is a large collaborative international academic randomized controlled
trial, designed to test the safety and efficacy of transdermal
glyceryl trinitrate (a
nitric oxide donor) in 5000 patients when given within 48 hours of stroke
onset. Patients who are taking antihypertensive therapy at the time of their
stroke will also be randomized to continue or temporarily stop this. The
primary end point is combined death or dependency (modified Rankin Scale 3 to
6) at 3 months, to be assessed centrally by telephone. Subgroup analyses will
include efficacy in patients with: ischemic stroke, high blood pressure
(systolic blood pressure >160 mm|Hg), and
treatment <12 hours. Randomization and data registration are performed over
the Internet. Centers are invited to join the collaborative group. 988 patients
had been recruited by August 2008.
Principal Investigator: Philip M.W. Bath, MD FRCP
Contact: P.M.W. Bath, ENOS Trial Centre, Division of Stroke
Medicine, University of Nottingham, City Hospital Campus, Nottingham NG5 1PB,
UK. Phone 44-115-823-1768. Fax
44-115-823-1767. E-mail: enos@nottingham.ac.uk Internet:
http://www.enos.ac.uk/
Location: Global
Number of Centers: 66 (looking for 200) from 13 countries
Sponsor: UK Medical Research Council (previously BUPA
Foundation, The Hypertension Trust,
Dates of Study: July 2001 to October 2011
Evaluation of the STARflex Septal Closure System in Patients with a Stroke or Transient Ischemic Attack due to Presumed Paradoxical Embolism through a PFO (CLOSURE)
CLOSURE is a prospective, multicenter, randomized
controlled trial to evaluate the safety and efficacy of the STARflex
Septal Closure System versus aspirin and/or warfarin therapy for the prevention of stroke, TIA and
mortality in patients with an initial stroke or TIA due to a presumed
paradoxical embolism through a patent foramen ovale
(PFO). The goal is to determine whether device closure of a PFO is superior to
best medical therapy for preventing recurrent stroke or TIA in patients with an
initial cryptogenic stroke/TIA and a PFO. Sixteen hundred patients (800 in each
group) at up to 100 sites nationally will be randomized within 180 days of the
entry event. Study patients will be followed for 2 years. All strokes and TIAs will be adjudicated by a blinded Clinical Events
Committee using prespecified clinical and MR imaging
definitions. The primary end point of incidence of 24-month stroke or TIA, all
cause mortality for the first 30 days of follow-up or hospital discharge, whichever
is longer, and neurological mortality from ≥ 31 days of follow-up will be
analyzed on an intent-to-treat basis using the c2 test and logistic
regression adjusting for study center and demographic characteristics deemed
related to the primary end point. Safety analyses will focus on the incidence
of severe adverse events related to either device insertion or major bleeding
complications on medical therapy.
Principal Investigator: Anthony J. Furlan
MD
Co-Principal Investigator: Marc Reisman
MD
Executive Committee: A.J. Furlan, M. Reisman, H. Adams, L. Wechsler, Gregory Albers, Robert Felberg, M. Landzberg, H.
Hermann, Al Raizner, Saibal
Kar
Data Safety Monitoring Board: J. P. Mohr, Chairman
Clinical Events Committee: Marc Fisher, Chairman
Data Management: Harvard Clinical Research Institute
Contact: A.J. Furlan, Cleveland
Clinic Department of Neurology, S91, 9500 Euclid Avenue, Cleveland, Ohio 44195.
Fax 216 444 0232. Phone 216 444 5535. E-mail furlana@ccf.org.
Sponsor: NMT Medical,
Dates of Study: July 2003 to July 2006
The Field Administration of Stroke Therapy - Magnesium (FAST-MAG) Phase 3 Trial
Magnesium is neuroprotective in preclinical models
of stroke and has been safe and shown signals of potential efficacy when
administered early after onset in initial human stroke clinical trials. Delayed
initiation of neuroprotective agents has hindered
past phase 3 neuroprotective agent trials. The
purpose of the FAST-MAG phase 3 trial is to demonstrate that paramedic initiation
of intravenous magnesium sulfate within 2 hours of symptom onset improves the
long-term functional outcome of hyperacute stroke
patients. FAST-MAG is a multicenter, randomized,
double-blind, placebo-controlled phase 3 trial that will enroll 1298 patients
(649 in each arm). The study population consists of prehospital
patients with acute stroke, including both cerebral infarction and intracerebral hemorrhage patients. Inclusion criteria: (1)
likely stroke as identified by the Los Angeles Prehospital
Stroke Screen (LAPSS), (2) age 40 to 95, (3) symptom onset within 2 hours of
treatment initiation, (4) deficit present ³15 minutes. Study agent
will be started within 1 hour of onset in ≈1/2 of enrolled patients and
between 1 to 2 hours after onset in the remainder. Study sites are up to 80
ambulance-receiving hospitals in
Principal Investigator: Jeffrey L. Saver, MDM
Co-Principal Investigators: Sidney Starkman,
MD; Sam Stratton, MD; Chelsea Kidwell, MD; Marc Eckstein, MD
Contact: Jeffrey L. Saver, MD, Professor of Neurology, UCLA
Stroke Center, 710 Westwood Plaza, Los Angeles, CA 90095. Phone 310-794-6379.
Fax 310-267-2063. E-mail jsaver@ucla.edu
Location:
Sponsor: National Institute of Neurologic
Disorders and Stroke - National Institutes of Health
Dates of Study: 2003—2008
Increasing Stroke treatment through Interventional Behavior Change Tactics (INSTINCT)
The INcreasing Stroke Treatment through
Interactive behavioral Change Tactic (INSTINCT) trial is a multicenter,
randomized, controlled study designed to evaluate the effectiveness of a
standardized, system-based, barrier assessment and interactive educational
intervention (BA-IEI) approach to increase appropriate tPA
use in stroke. The intervention is based on adult education and behavior change
theory, targets emergency departments and hospital systems, and is designed for
replication in community health initiatives. It incorporates local stroke
champion development, hospital-specific barrier evaluation, mixed CME modules
targeting identified barriers, performance feedback, protocol development, and
academic detailing. The primary end point will be the increase in appropriate
use of tPA in stroke with
evaluations of change in emergency physician knowledge on tPA
use.
Principal Investigator: Phillip A. Scott, MD
Contact: Shirley Frederiksen, MS, RN,
Project Manager, 24 Frank Lloyd Wright Dr, Lobby H Box 381, Ann Arbor, MI
48106. Phone 734-232-2142.
Location:
Number of Centers: 24
Sponsor: National Institute for Neurological Disorders and
Stroke, National Institutes of Health.
Dates of Study: July 2005 to July 2010.
International Carotid Stenting Study (ICSS)
ICSS is a randomized, multicenter trial to compare
the risks of treatment and benefits in the prevention of stroke of primary
carotid stenting in comparison with conventional
carotid endarterectomy.
Principal Investigator: M.M. Brown, MD
Contact: Martin M. Brown, MD, FRCP, Professor of Stroke
Medicine, Institute of Neurology,
Location: Europe, North America,
Number of Centers: 52
Sponsor:
Dates of Study: Recruitment started in 2001
Web Address: www.cavatas.com
International Citicoline Trial on acUte Stroke (ICTUS)
Citicoline is a safe drug approved in some countries
for the treatment of acute ischemic stroke. The drug has shown some evidence of
efficacy given within 24 hours from symptoms onset in a pooled analysis, based
on 4 clinical trials done in the
Principal Investigator: Antoni Dávalos, MD, PhD
Trial Steering Committee: Antoni Dávalos, E (Chairman); José Alvarez-Sabín,
E; José Castillo, E; Erik Cobo, E (Statistician); Exuperio Díez-Tejedor, E; Jose
Ferro, P; Savion Gropper, E; Eduardo Martínez-Vila, E; Julio J Secades,
E.
Data Safety Monitoring Board: Kennedy R. Lees, UK (Chairman);
Werner Hacke, D; Steve Warach,
USA; John Whitehead UK (Statistician).
Contact: Dr Antoni Dávalos, Department of Neurosciences. Hospital
Germans Trias i Pujol, Crta. de Canyet, s/n, 08916
Location:
Sponsor: Ferrer Group S.A.
Registers: EudraCT Nº 2005-004825-25;
ClinicalTrials.gov NCT00331890; Stroke Trials Registry;
ww.thelancet.com/journals/lancet/misc/protocol/06PRT-3005.
Dates of Study: 2006 to 2010. 471 patients were included by
March 31, 2008.
Intra-Arterial Versus Intravenous Thrombolysis In Acute Ischemic Stroke (SYNTHESIS EXPANSION)
The trial has entered a new phase with a grant from the Italian Agency for
Drugs (AIFA Agenzia Italiana
del Farmaco) now financing it. In this new phase, the
name has turned into SYNTHESIS EXPANSION; a web-based data collection and
randomization system has been implemented and the protocol has undergone
refinements as far as the intraarterial procedure.
SYNTHESIS EXPANSION remains a multicenter RCT,
open-label, with blinded follow-up aiming to determine whether locoregional intra-arterial (IA) alteplase
(in the new protocol, "alone, associated to, or substituted by mechanical recanalization manouvres"),
as compared with systemic intravenous (IV) infusion of the same drug within 3
hours of ischemic stroke, increases the proportion of independent survivors at
3 months. Eligibility still applies to patients with symptomatic, CT verified,
acute ischemic strokes being able to initiate IV alteplase
within 3 hours and IA procedure within 6 hours of stroke onset when uncertainty
about appropriateness of the 2 approaches exists as established by the treating
physician. Eligible patients are randomized to receive either 0.9 mg/kg (max 90
mg) IV alteplase (control arm) or to receive up to
0.9 mg/kg IA alteplase (max 90 mg) over 60 minutes
into the thrombus and/or to undergo a mechanical recanalization
procedure (clot mechanical disruption and/or retrieval, PTA stenting
of the occluded artery or of disclosed underlying stenotic
lesion). The study remains designed to detect or disprove (a=5%
and power probability=80%) a 15% absolute difference between the treatment
groups in the percentage of patients with a favourable
outcome (modified Rankin Scale score 0 to 1). Enrollment will still be
completed with 350 randomized patients.
Principal Investigator: A. Ciccone
Safety and Monitoring Committee: L. Candelise,
G. Del Zoppo, P. Sandercock.
Monitor: E. Botto
Follow-Up: T. Cantisani
Contact: Alfonso Ciccone, Stroke
Unit, Ospedale "Niguarda Ca' Granda", Piazza
Ospedale Maggiore 3, 20164
Location:
Number of Centers: 14 centers are currently authorized for
recruitment; 4 centers have expressed interest or are in the process of
application to local ethical committees; investigators from other centers are
invited to participate.
Sponsor: Grant from AIFA (Agenzia Italiana del Farmaco).
Dates of Study: SYNTHESIS ended in January 2008 with 54
recruited patients (15% of the total). Its results are in the process of being
published. Recruitment for SYNTHESIS EXPANSION has started February 1st 2008
and 11 patients (over 22 considered eligible) have been randomized up to now.
Locomotor Experience Applied Post-Stroke (LEAPS)
Locomotor training using body weight support and a
treadmill as a therapeutic modality for the rehabilitation of walking
post-stroke is being rapidly adopted into clinical practice. A 2005 Cochrane
review highlighted the urgent need for a well-designed trial to determine the
effectiveness of this intervention. The objective of the Locomotor
Experience Applied Post-Stroke (LEAPS) trial is to determine if there is a
difference in the proportion of participants who successfully recover walking
ability at one year post stroke when individuals are randomized to a
specialized locomotor training program (LTP),
conducted at 2- or 6-months post-stroke, or those randomized to a home based
non-specific, low intensity exercise intervention (HEP) provided at 2 months
post-stroke. The LTP program includes use of body weight support on a treadmill
and overground training. The LTP and HEP
interventions are delivered for 36 sessions over 12 weeks. Successful walking
recovery is defined as the achievement of a 0.4 m/s gait speed or greater by
persons with initial severe gait impairment (< 0.4 m/s), or the achievement
of a 0.8 m/s gait speed or greater by persons with initial moderate gait
impairment (≥ 0.4 m/s - < 0.8 m/s). We will also determine if the
timing of LTP delivery (early vs. late) affects the improvement in gait speed
at 1 year and whether initial locomotor impairment
severity interacts with the timing of LTP delivery. The effect of number of
treatment sessions will be determined by changes in gait speed taken
pre-treatment, post-12, post-24, and post-36 sessions. We will recruit 400
adults, with moderate or severe walking limitations, within 45 days of their
stroke onset. Participants are followed until 2 months post stroke to establish
eligibility. At 2 months participants who continue to be eligible, undergo
baseline assessment. After baseline assessment, participants are stratified by locomotor impairment severity as determined by overground walking speed and randomly assigned to one of
three groups: (a) LTP-Early; (b) LTP-Late or (c) Home-based Exercise
Program-Early.
Principal Investigator: Pamela W. Duncan, Ph.D., FAPTA
LEAPS Data Management and Analysis Center: Stanley Azen, Ph.D.
Steering Committee: Pamela W. Duncan, PhD, FAPTA (PI), Andrea
Behrman, PhD, PT (Co-PI), Katherine Sullivan, PhD (Co-PI), Steven Nadeau, MD,
Bruce Dobkin, MD, Samuel S. Wu, PhD, and Sarah Hayden
Data Safety Monitoring Board: Bruce Coull,
MD (Chair), Elizabeth A. Noser, MD, Michael Parides, PhD, and Steven Wolf, PhD, PT Medical
Safety Monitor: Alexander Dromerick, MD
Contact: Pamela W. Duncan, Ph.D.; LEAPS Administrative
Coordinating Center, Duke University, 2200 West Main Street, Suite 220, Durham,
NC 27705; phone: 919-286-3399 ext 235; fax 919-286-5601
Location: LEAPS Administrative Coordinating Center: Duke
University, Durham, NC; Data Management and Analysis Center: University of
Southern California, Los Angeles, CA; Clinical Coordinating Centers: University
of Florida, Gainesville, FL and University of Southern California, Los Angeles,
CA; Clinical Intervention Sites: Brooks Rehabilitation Hospital, Jacksonville,
FL; Florida Hospital, Orlando, FL; Long Beach Memorial Hospital, Long Beach,
CA; Sharp Rehabilitation Center, San Diego, CA; and USC PT Associates, Los
Angeles, CA.
Number of Centers: 5 clinical intervention sites currently
enrolling participants.
Sponsors: National Institute of Neurological Disorders and
Stroke and the
Dates of Study: September 2005 through June 2010.
Web Address : http://leaps.usc.edu/
Clinical Trial Registration: ClinicalTrials.gov NCT00243919
Magnesium in Aneurysmal Subarachnoid Hemorrhage (MASH-II)
The MASH-II study is a phase III randomized, international multicenter trial to determine whether magnesium reduces
the frequency of poor outcome (death or dependence) in patients admitted within
4 days after aneurysmal subarachnoid
hemorrhage. Magnesium sulfate 64 mmol/day (equals 16
grams/day) or placebo intravenously is started as soon as possible after
informed consent and continued until 20 days after the hemorrhage. We plan to
include 1200 patients in 5 years. Outcome will be assessed after 3 months by
means of the modified Rankin score.
Principal Investigators: Walter M. van den Bergh; Gabriel J.E. Rinkel
Steering Committee: S.M. Dorhout Mees, MD, W.M. van den Bergh, MD; A. Algra,
MD; G.J.F. Brekelmans, MD; J. van Gijn,
MD; F. van Kooten, MD; P.M. Lavados,
MD; R.J. van Oostenbrugge, MD; G.J.E. Rinkel, MD; R. Al-Shahi Salman, MD; W.P. Vandertop, MD;
M. Vermeulen, MD (New members may be added if more
(international) centers join the study).
Data Monitoring Committee: J.G. van der
Bom (chair); W.P.Th.M.
Contact: Sanne M. Dorhout
Mees, MD, Department of Neurology G03.224, University
Medical Center Utrecht,
Number of Randomizing Centers: 8
Number of Randomized Patients: 575
Sponsor: The Netherlands Heart Foundation (grant number:
2005B016)
Dates of Study: Randomization was started in January 2004.
Analysis of the results is planned in 2010.
ISRCTN#: 68742385
EudraCT#: 2006-003523-36
MR and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE)
The general aim of the MR RESCUE Trial is to investigate whether
diffusion-perfusion MRI can identify patients who will benefit substantially
from mechanical embolectomy with the Concentric Clot
Retriever device for the treatment of acute ischemic stroke up to 8 hours from
symptom onset. MR RESCUE is a randomized, controlled, blinded-outcome phase IIB
clinical trial. The trial pulls from the population of eligible acute ischemic
stroke patients with large vessel
Steering Committee: Chelsea Kidwell, Georgetown Univ, WHC Stroke Ctr, UCLA Dept
of Neurology, Washington, DC; Reza Jahan, Sidney Starkman, Jeffry Alger, Judy Guzy,
UCLA Stroke Ctr, Los Angeles, CA; Margy
McCullough-Hicks, Georgetown University; Timothy Schaewe,
UCLA Stroke Ctr, Washington, DC; Jeffrey Saver, UCLA
Stroke Ctr, Los Angeles, CA
Contact: Judy Guzy,
jguzy@mednet.ucla.edu 310.794.0591; Margy
McCullough-Hicks, mm883@georgetown.edu, 202.687.5396
Location: UCLA Stroke Network, 924 Westwood Blvd, #300, Los
Angeles, CA 90024-1777; Phone: 310-794-0600; Fax: 310-794-0599
Georgetown University Department of Neurology, 4000 Reservoir Rd., Building D
Suite 150, Washington, D.C. 20007; Phone: 202.687.5289; Fax: 202.687.8684
Number of Centers: 27 (20 actively enrolling)
Sponsors: NIH/NINDS, NINDS Grant Number P50 NS44378, S,B
Dates of Study: Commenced May 2004 (continuing)
Optimizing the Analysis of Stroke Trials (OAST)
Most trials in acute stroke have been neutral (or even negative). One
possible explanation is that they may have been analyzed suboptimally.
Functional outcome is usually scored using ordinal scales (eg,
modified Rankin Scale [mRS], Barthel
Index) and yet analyses are often based on dichotomization of the data (eg, mRS
0 to 2 vs 3 to 6), a process that would be expected
to reduce statistical power. We are comparing a variety of ordinal and nominal
statistical approaches using individual patient data from interventions which
modify outcome (either positively or negatively) in acute stroke or stroke
rehabilitation; neutral trial data from neutral interventions will not be
included. The aim is to identify one (or more) optimal approach(es) for use in future stroke trials. Authors of relevant
trials who are willing to share their trial data are invited to contact the
investigators.
Contact: Philip M.W. Bath, FRCP; Division of Stroke Medicine,
Location:
Number of Centers: Those centers that have organized a positive
or negative randomized controlled trial in acute stroke or stroke
rehabilitation
Sponsor: The Stroke Association (UK)
Dates of Study: October 2004 (continuing)
Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard-of-Care Treatment (RESPECT) Trial
PURPOSE: To investigate whether percutaneous PFO
closure is superior to current standard-of-care medical treatment in the
prevention of recurrent embolic stroke. DESIGN: Multicenter,
randomized, active control, blinded adjudicated outcome, clinical trial. SAMPLE SIZE: 710 patients (355 per study arm). POPULATION
STUDIED: Patients aged 18 to 60 years with patent foramen ovale
(PFO) who have had a cryptogenic stroke due to presumed paradoxical embolism
within the last 270 days. INTERVENTIONS: Patients are randomly assigned to
medical therapy or PFO closure with the AMPLATZER PFO Occluder.
Medical therapy options include aspirin alone, coumadin
alone, clopidogrel alone, or aspirin combined with
extended-release dipyridamole. OUTCOME MEASURES: The
primary end point is recurrent nonfatal stroke, all-cause postrandomization
death within 45 days of randomization or 30 days after implant, whichever
occurs last, or fatal ischemic stroke. The secondary
efficacy end points are complete closure of the defect at the 6-month
follow-up, time to recurrent symptomatic cryptogenic nonfatal stroke or
cardiovascular death, and transient ischemic attack. The primary safety end
point is all major adverse events. STATISTICAL ANALYSIS: The superiority of the
device will be tested by using an exact binomial test of the proportion of device
primary end point events to primary end point events across both arms of the
study, conditioned on the total number of events.
Steering Committee Members: John Carroll, MD, University of
Colorado School of Medicine, Denver, Colo; Jeffrey
Saver, MD, UCLA, Los Angeles, Calif; Richard Smalling, University of Texas Houston, Houston, Tex; David Thaler, TUFTS - NEMC, Boston, Mass.
Contact: Jeffrey L. Saver, MD, Professor of Neurology, UCLA
Stroke Center, 710 Westwood Plaza, Los Angeles, CA 90095. Phone: 310-794-6379
Fax: 310-267-2063. E-mail jsaver@ucla.edu
Number of Centers: 60 sites in the
Sponsor: AGA Medical Corporation,
Dates of Study: August 2003—Ongoing
Scandinavian Candesartan Acute Stroke Trial (SCAST)
SCAST is an international randomizing, placebo-controlled, double-blind
trial of candesartan (an angiotensin
receptor blocker) in acute stroke. Patients presenting within 30 hours of
stroke (ischemic or hemorrhagic) and with systolic blood pressure ≥140 mm|Hg 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: (1) death or major
disability at 6 months; (2) vascular death, myocardial infarction or stroke
during the first 6 months. Target recruitment: 2500 patients by mid-2009.
Coordinating Investigator: Eivind
Berge, MD, PhD
Contact: Else Charlotte Sandset, MD,
Trial Manager, Phone +4722119911, Fax: +4722119912, E-mail: scast@scast.no
Location: SCAST, Ullevaal University
Hospital, NO-0407 Oslo, Norway
Number of Centers: 150+
Sponsors: Basic funding from Norwegian health authorities. Trial drugs and limited, unconditional grants from AstraZeneca.
Dates of Study: Start of recruitment: 2005. End of recruitment:
around mid-2009. End of follow-up: Late-2009
Siblings With Ischemic Stroke Study (SWISS)
Cohort and twins studies suggest that there is an important genetic
component to the overall risk of acquiring ischemic stroke. SWISS is a prospective,
multicentered clinical investigation to search for
chromosomal regions of interest that harbor stroke susceptibility genes. A microsatellite genome-wide screen will be carried out using
DNA collected in this study from sibships consisting
of a proband with ischemic stroke and one or more
concordant sibling with or without discordant siblings. Three hundred
concordant sibling pairs and 200 discordant siblings (800 total study subjects)
will be enrolled. A genotype-blinded central committee adjudicates concordance
and discordance for ischemic stroke in siblings. Probands
are enrolled at participating clinical centers. Probands
are potentially eligible for SWISS if they are diagnosed by a study neurologist
as having had a CT- or MRI-confirmed ischemic stroke, have at least 1 living
sibling with a history of stroke, and are at least 18 years old. Probands are excluded if the index stroke occurred within
48 hours after an invasive cerebrovascular or
cardiovascular procedure or within 60 days after a nontraumatic
subarachnoid hemorrhage. Also excluded are subjects
with brain biopsy-proven CNS vasculitis, mechanical
aortic valve, mechanical mitral valve, bacterial endocarditis, CADASIL, Fabry's
disease, homocystinuria, MELAS, or sickle cell
disease. As of August 4, 2008, 287 stroke-affected sibling pairs had been
enrolled.
Principal Investigator: James F. Meschia,
MD
Contact: Alexa Richie, Clinical
Research Coordinator, Mayo Clinic, 4500 San Pablo Road, 2 East Cannaday Bldg, Jacksonville, FL 32224. Phone 904-296-3815.
Fax 904-953-6036. E-mail Richie.alexa@mayo.edu
Location: Stroke Verification Committee: Department of
Neurology, Mayo Clinic,
Statistical Coordinating Center: Department of Biostatistics,
Number of Centers: 53
Sponsor: National Institute of Neurological Disorders and
Stroke, National Institutes of Health
Dates of Study: Ongoing
Surgical Trial in Lobar Intracerebral Haemorrhage (STICH II)
This is an international multicenter trial to
determine whether a policy of "early surgical evacuation" of the hematoma in patients with spontaneous supratentorial
lobar intracerebral hemorrhage only will improve
outcome compared with a policy of "initial conservative treatment."
Primary outcome is mortality and morbidity at 6 months as measured by the
Glasgow Outcome Scale. Secondary outcome instruments include the modified
Rankin Scale, EuroQol and the Barthe1 Index. The
trial will also help to better define the indications for surgery. In total 600
patients, for whom the surgeon is in equipoise about the need for surgical
evacuation, will be randomized to receive "early surgery" (within 12
hours of randomization), preferably using craniotomy, or "initial
conservative treatment." Patient status is recorded 2 weeks after
randomization and then outcome is assessed at 6 months using a structured
postal questionnaire to the subject or subject's relative to ensure assessor
blindness. Funding for this trial was activated in September 2006, and as of
March 31, 2008, 42 patients and 40 centers had been recruited. Center
recruitment is ongoing. Please visit the website if you would like to take
part.
Principal Investigators: Prof A.D. Mendelow,
Dr B.A. Gregson, Mr P.M.
Mitchell, Prof G.D. Murray and Dr A.R. Gholkar
Contact: Dr Barbara Gregson, Trial
Director. Phone: 44-191-256-3139. Fax: 44-19l-256-3268. E-mail: stich@ncl.ac.uk
Location: STICH Office, Ward 31, North Wing, Newcastle General
Hospital, Westgate Road, Newcastle upon Tyne, NE4 6BE, UK. Website: www.ncl.ac.uk/stich
Number of Centers: 40
Funder: Medical
Research Council (UK)
Sponsor: Newcastle upon Tyne Hospitals NHS Trust
ISRCTN: ISRCTN22153967
Dates of Study: 2006 to 2010
Third International Stroke Trial (IST-3)
Background: For every 1000 patients with acute stroke treated with
intravenous recombinant tissue plasminogen activator
(IV rt-PA) within 6 hours of stroke onset, 55 avoid
death or dependence, yet few patients are being treated worldwide. The third
International Stroke Trial (IST-3) aims to provide more reliable evidence on
which categories of patients benefit most from IV rt-PA
and how it could be more widely used. Study Design: IST-3 is an international, multicenter, randomized, controlled, postlicensing
trial of IV rt-PA (0.9 mg/kg) for acute ischemic
stroke, with a PROBE (Prospective, Randomized, Open, Blinded Endpoint) design.
Patient Eligibility: Eligible patients must be assessed and able to start
treatment within 6 hours of onset, and a CT (or MR) scan must have excluded
intracranial haemorrhage. Details of
inclusion/exclusion criteria are given in the trial protocol. Center
Eligibility: To join the study, centers must have an established acute stroke
service which meets predefined criteria. Trial Procedures: are very efficient
and aim to ensure trial treatment is started with minimal delay. Patient
inclusion is by telephone call to a rapid centralized randomization system
which balances on key prognostic factors. Trial treatment is only allocated by
the system after the baseline data have been successfully recorded and
cross-checked. Brain imaging (CT or MR) must be repeated after treatment (at 24
to 48 hours). An international expert panel reviews 'blinded' all baseline and
follow-up CT/MR images by means of an innovative centralized web-based image-reading
system (see ACCESS study for details). In all centers, follow-up is conducted
by centralized (blinded) postal or telephone questionnaire, conducted
independently of the clinician treating the patient. Trial Outcome Measures:
The primary measure of outcome is death or dependence at 6 months (poor
functional outcome). A number of secondary outcomes are specified in the
protocol. Planned subgroup analyses will include an assessment of the effect
of: age, stroke severity, time to randomization, CT
appearances, blood pressure and other factors on the risks and benefits of
treatment. Sample Size: With 1000 patients the trial is powered to detect a 7%
absolute difference in the primary outcome. With 3500 patients, the trial could
detect a 4% absolute difference in the primary outcome, and with 6000 patients,
mostly treated between 3 and 6 hours of onset, the trial could detect a 3%
absolute difference in the primary outcome. Study Progress: A total of 1225
patients had been recruited by July 29, 2008.
Trial Coprincipal Investigators: Richard
Lindley and Peter Sandercock.
Imaging Principal Investigator: Joanna Wardlaw
Contact: Professor Peter Sandercock,
Department of Clinical Neurosciences,
Location:
Number of Centers: Currently 85; new centers are welcome to
join.
Sponsor: The study is an investigator led trial. The
ISRCTN: ISRCTN25765518
Dates of Study: 2001-2012.
Trial on Endovascular Aneurysm Management (TEAM)
The management of patients with unruptured
aneurysms remains controversial. Patients with unruptured
aneurysms may experience intracranial haemorrhage,
but the incidence of this event is still debated. Endovascular treatment can
prevent rupture but involves immediate risks. Furthermore, successful treatment
does not eliminate all risks. Hence, the balance of the risks and benefits is
uncertain. TEAM (for Trial on Endovascular Aneurysm Management) is an
international, randomized, multicenter, controlled
trial comparing the combined mortality and morbidity (modified Rankin Scale [mRS] ³3) from intracranial hemorrhage in patients with unruptured aneurysms treated by conservative management (or
deferral for 10 years or until definite indications are thought to have arisen)
as compared to endovascular coiling. Secondary end points will include the incidence
of hemorrhagic events in both groups, the morbidity related to endovascular
coiling, morphological results at 5 and 10 years, overall clinical outcome at 5
and 10 years, quality of life assessment, and the level of distress caused by
the knowledge of the hemorrhagic risk. To take into account ease of
recruitment, feasibility, generalizability, and
ethical considerations, entry criteria will be minimized. The analyses will be
performed on 2 populations: intent-to-treat and per protocol. The main statistical
tests will involve comparisons between the 5- and 10-year probabilities of poor
outcomes (mRS ³3): (1) from hemorrhage
related to the lesion, excluding per operative complications, (2) the 5/10-year
probabilities of mortality from hemorrhage or from complications of treatment,
or (3) comparisons of the 5- and 10-year probabilities of combined disease or
treatment-related mortality and morbidity, in the absence of other causes of
death or disability. Other analyses will involve Kaplan-Meier life-table
methods to assess the 5- and 10-year mortality from intracranial bleeding or
from treatment among all those allocated immediate coiling (including the few
who did not undergo it) and all those allocated deferral of any intervention
(including the few who will eventually be operated on) as well as overall
mortality. The study will be conducted in 60 international centers. The entire
study will enroll ≈2002 patients equally divided between the 2 groups, a
size sufficient to achieve 80% power at a 0.0167 significance to detect
differences in (1) disease or treatment-related poor outcomes from 7%-9% to
3%-5%; (2) overall mortality from 16% to 11%. The duration forecast of the
study is 14 years, the first 3 years being for patient recruitment plus a
minimum of 10 years of follow-up.
Principal Investigator: Dr Jean Raymond, MD
Steering Committee: Dr Andrew Molyneux,
MD,UK; Professeur Jacques Moret,
MD, France; Dr Herman Zeumer, MD, Germany; Dr
Alejandro Berenstein, MD, USA; In Sup Choi, MD, USA; Cameron McDougall, MD, USA; Gabriel Rinkel, MD, The Netherlands; Claiborne Johnston, MD, PhD,
USA; Dr Jean Raymond, MD, Canada; Dr Isabelle Rouleau,
PhD, Canada; Dr Allan J. Fox, MD, Canada; Dr Jean-Paul Collet,
MD, PhD, Canada; Dr Yves Lepage, PhD, Canada.
Contact: Guylaine Gevry,
Interventional Neuroradiology Clinical Research Unit
(NRI-CRU),1560
Location:
Number of Centers: 60 in total. 33 are already active.
Interested centers may still join in.
Sponsor: Canadian Institutes of Health Research (CIHR)
Dates of Study: Recruitment 2006-2010; follow-up until 2020
VITAmins TO Prevent Stroke (VITATOPS)
The VITATOPS study is a multicenter, randomized,
double blind, placebo-controlled secondary stroke prevention trial to determine
whether the addition of vitamin supplements (B12 500 mg, B6 25 mg, Folate 2 mg) to best medical/surgical management (including
modification of risk factors) will reduce the combined incidence of recurrent
vascular events (stroke, myocardial infarction) and vascular death in patients
with recent stroke or transient ischemic attack (TIA). All patients presenting
to one of the participating neurologists or general physicians within 7 months
of stroke (ischemic or hemorrhagic) or TIA (eye or brain) are eligible for this
trial. Eligible patients will be randomized in a double-blind fashion to
receive multivitamins or placebo, 1 tablet daily. The primary outcome event is
the composite event "stroke, myocardial infarction, or death from any
vascular cause", whichever occurs first. Our target is to recruit a total
of 8000 patients with a median follow-up of 2.5 years. Recruitment to the trial
began in November 1998 and is planned to continue until 2008. We aim to
complete final follow-up by 2009. However, the Steering Committee will be
flexible in dictating the need for ongoing recruitment and continuing
follow-up, depending on the overall rate of the primary outcome event in the
entire cohort at each interim analysis.
Steering Committee (alphabetically): Dr Ross Baker, Dr John Eikelboom, Ms Anna Gelavis, Prof
Graeme Hankey (Chairman), Mrs
Siobhan Hickling, Prof Konrad
Jamrozik, A/Prof Francesco van Bockxmeer
Contact: VITATOPS Trial Office, Stroke Unit, Royal Perth
Hospital, Wellington St Perth 6001, Australia. Phone +61 8
9224 7004. Fax +61 8 9224 8424. E-mail: VITATOPS@health.wa.gov.au. Website:
http://vitatops.highway1.com.au
Centers: Australia (16), Austria (1), Belgium (1), Brazil (1),
Hong Kong (2), India (23), Italy (8), Malaysia (2), Moldova (1), Netherlands
(3), New Zealand (5), Pakistan (3), Philippines (8), Portugal (4), Republic of
Georgia (1), Serbia & Monte Negro (2), Singapore (1), Sri Lanka (2), United
Kingdom (29) and United States (5) and actively seeking centers worldwide.
Dates of Study: 1998 – 2009
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