Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence (FASTER)

Sponsor

University of Calgary (Other)

Overall Status

Completed

CT.gov ID

NCT00109382

Collaborator

Canadian Institutes of Health Research (CIHR) (Other), Canadian Stroke Consortium (CSC) (Other)

500

Enrollment

Locations

45.1

Duration (Months)

27.8

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Current management of patients with TIA (transient ischemic attack) or minor stroke includes the prompt investigation and treatment in the days and weeks after the event. However, new evidence shows patients are at the highest risk of stroke in the first few days after the TIA, with 50% of strokes which happen in the three months following TIA occurring within 48-72 hours. To date, there is no evidence to guide physicians on how to safely reduce this risk.

The FASTER trial is focusing on the initial period of high risk, starting patients on stroke prevention treatments in the hours following a TIA or minor stroke. The drugs to be tested have been shown to be effective in the similar setting of cardiology, reducing recurrent cardiac events in patients with unstable angina when commenced with the same speed after an event.

All patients will be on aspirin. The trial will see if adding another drug, clopidogrel, has an additional benefit in reducing the number of strokes after TIA or minor stroke within three months of TIA or minor stroke. It will also look if the very early introduction of simvastatin, a cholesterol lowering therapy, reduces stroke after TIA or minor stroke, both by itself and in addition to clopidogrel. The final aim of the trial is to ensure that these treatments are safe to be used in this population of patients.

Condition or Disease	Intervention/Treatment	Phase
Transient Ischemic Attack Stroke	Drug: Aspirin Drug: Clopidogrel Drug: Simvastatin	Phase 2/Phase 3

Detailed Description

The Fast Assessment of Stroke and Transient ischemic attack to prevent Early Recurrence (FASTER) is a randomized clinical trial designed to investigate the effect of hyper-acute initiation of stroke prevention treatments in patients with a minor stroke or transient ischemic attack (TIA).

This group of individuals has been recognized as being at high risk of recurrent events. Johnston et al. (2000) were the first to suggest that the risk of stroke after TIA was front-loaded in the first few days. This has been confirmed elsewhere with Lovett et al. (2003) having shown in the Oxfordshire Community Stroke Project that the 7-day risk of recurrent stroke was 8.6%, and a 30-day risk of 12.0%. These findings are similarly found in the Oxford Vascular Study; 8.0% and 11.5% respectively for a recurrent event (Coull et al., 2004). The NASCET (North American Symptomatic Carotid Endarterectomy Trial) study also supports the finding of high risk of early recurrent stroke. 8.5% of patients with a hemispheric TIA suffered a recurrent stroke within one week rising to 20% at 90-days (Eliasziw et al., 2004). This data suggest that patients with carotid stenosis are at the highest risk of early recurrent stoke.

Only one in four patients with acute ischemic stroke presenting within three hours of symptom onset are being treated with t-PA (Barber et al., 2001). The most common reason for exclusion from treatment is that a patient's deficit will be too mild for treatment or will have completely resolved thereby not meriting the risks of treatment with tPA. These are the patients that have a higher risk of early recurrence. The clinical imperative is to identify hyper-acute treatment strategies to minimize that risk.

FASTER is a double blind, randomized controlled trial with a 2x2 factorial design with patients followed for 90-days. Patients will be randomized within 24 hours of symptom onset to one of four possible treatment arms:

Aspirin
Aspirin and Clopidogrel
Aspirin and Simvastatin
Aspirin and Clopidogrel and Simvastatin

Study Hypotheses

A rapid commencement of clopidogrel plus aspirin within 24 hours of acute TIA or minor stroke is more effective than aspirin in reducing the 90-day risk of stroke by an absolute difference of 2%.
A rapid commencement of simvastatin plus aspirin within 24 hours of acute TIA or minor stroke is more effective than aspirin in reducing the 90-day risk of stroke by an absolute difference of 2%.
A rapid commencement of clopidogrel plus aspirin plus simvastatin within 24 hours of acute TIA or minor stroke is more effective than aspirin alone in reducing the 90-day risk of stroke by an absolute difference of 4%.
The incidence of adverse events is not different among treatment groups.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Double

Primary Purpose:

Prevention

Official Title:

Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence (FASTER)

Study Start Date :

May 1, 2003

Actual Study Completion Date :

Feb 1, 2007

Outcome Measures

Primary Outcome Measures

Any stroke at 90 days []
Stroke severity []

Secondary Outcome Measures

Composite of stroke []
Myocardial infarction []
Vascular death at 90 days []

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with TIA or minor acute ischemic stroke (NIHSS < 4 at the time of randomization) who must NOT be candidates for acute thrombolysis or other acute intervention indicated as the current standard of care
Aged 40 years or older
Patients with: (a) weakness at time of TIA/minor stroke and/or language disturbance at time of TIA/minor stroke and; (b) duration of neurological deficit (TIA) > 5 minutes
Patients can be randomized within 24 hours of symptom onset. Symptom onset is defined by the "last seen well" principle
Patients must have provided written, informed consent to participate in the FASTER trial.

Exclusion Criteria:

Patients with pure sensory symptoms, pure vertigo or dizziness, pure ataxia or pure visual loss
Patients for whom thrombolysis or other acute intervention is indicated as the current standard of care
Patients who are currently on statin therapy, antiplatelet therapy (not including aspirin), or long-term non-steroidal anti-inflammatory drugs (NSAIDs but not COX inhibitors), or anticoagulation
Patients who in the opinion of the site Investigator, should be commenced on statin therapy
Patients with neurological deficit due to intracranial hemorrhage (intracranial hemorrhage, subarachnoid hemorrhage, subdural hematoma, epidural hematoma), tumor, infection or any finding not consistent with acute brain ischemia as the cause of presenting symptoms
Presumed cardiac source of embolus (e.g. atrial fibrillation, prosthetic cardiac valve, known/suspected endocarditis)
Patient with a concomitant acute coronary syndrome (acute myocardial infarction or unstable angina)
Modified Rankin Score 3 or more (pre-morbid historical assessment)
Patients in whom the qualifying event was due to a complication of cerebral angiography, a revascularization procedure or trauma
Uncontrolled hypertension at baseline (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg), or malignant hypertension defined by brain plus acute organ involvement due to acute hypertension
Women who are breast-feeding or pregnant. Women of childbearing potential must have a negative pregnancy test prior to randomization. Women of childbearing potential may still participate in the trial but must plan on not becoming pregnant during the course of the study and must practice a suitable method of birth control. If a patient becomes pregnant or begins breast-feeding during the study, both study drugs will be discontinued immediately, and the patient followed for the duration of the study
Evidence of contraindication for use of Trial Medication: (i) serious systemic bleeding precluding antiplatelet therapy; (ii) hypersensitivity to aspirin, thienopyridine drugs (clopidogrel or ticlopidine) or statins; (iii) current or past history of renal insufficiency [serum Creatinine >150 umol]; (iv) hepatic dysfunction indicated by any or all of the following [ALT >3xULN, AST >3xULN, ALP >3xULN]; (v) thrombocytopenia [platelet count < 150 x10^{9/L]; (vi) neutropenia [neutrophil count <
0.5 x10}9/L]; (vii) bleeding diathesis or coagulopathy indicated by any or all of the following [INR >1.2, PT >1.2xULN, PTT >1.2xULN]
Life expectancy of less than 90 days
Participation in another clinical therapeutic trial (drug or device) either concurrently or within the previous 30 days, or prior participation in FASTER
Geographical or other factors that render follow-up impractical or that render evaluation of outcome events impossible (e.g. severe dementia). Patients may be randomized who could and are willing to complete their follow-up at a participating centre

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
2	Foothills Medical Centre	Calgary	Alberta	Canada	T2N 2T9
3	Universtiy of Alberta Walter MacKenzie Health Sciences Centre	Edmonton	Alberta	Canada	T6G 2B7
4	University of Lethbridge Hospital	Lethbridge	Alberta	Canada	T1J 0N9
5	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 3J5
6	St. Paul's Hospital	Vancouver	British Columbia	Canada	V6Z 1Y6
7	Centre for Stroke Research	Victoria	British Columbia	Canada	V8R 4R4
8	St. John Regional Hospital	Saint John	New Brunswick	Canada	E2L 4L2
9	Queen Elizabeth ll Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 3A7
10	London Health Sciences Centre - University Hospital	London	Ontario	Canada	N5A 5A5
11	Trillium Health Centre	Mississauga	Ontario	Canada	L5B 4A2
12	Ottawa Hospital	Ottawa	Ontario	Canada	K1H 8L6
13	Sunnybrook Women's Health Centrre	Toronto	Ontario	Canada	M4N 3M5
14	St. Mike's Hospital	Toronto	Ontario	Canada	M5C 1R6
15	Toronto Western Hospital -University Health Network	Toronto	Ontario	Canada	M5T 2S8
16	Chicoutimi Hospital	Chicoutimi	Quebec	Canada	G7H 6B9
17	Hopital Charles LeMoyne	Greenfield Park	Quebec	Canada	J4V 2H1
18	Hopital Notre-Dame du CHUM	Montreal	Quebec	Canada	H2L 4M1

Sponsors and Collaborators

University of Calgary
Canadian Institutes of Health Research (CIHR)
Canadian Stroke Consortium (CSC)

Investigators

Principal Investigator: Alastair M Buchan, Dept of Clinical Neurosciences, University of Calgary
Study Director: James Kennedy, Nuffield Dept of Clinical Medicine, University of Oxford