Clinical Trial

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. 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%.

B. 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%.

C. 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%.

D. The incidence of adverse events is not different among treatment groups.

Eligibility
Ages Eligible for Study: 40 Years and older
Genders Eligible for Study: Both

Criteria

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.



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




Publications indexed to this study:

Kennedy J, Hill MD, Ryckborst KJ, Eliasziw M, Demchuk AM, Buchan AM; FASTER Investigators. Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial. Lancet Neurol. 2007 Nov;6(11):961-9. Epub 2007 Oct 10.



Study placed in the following topic categories:
Ischemic Attack, Transient
Cerebral Infarction
Simvastatin
Vascular Diseases
Central Nervous System Diseases
Ischemia
Brain Diseases
Cerebrovascular Disorders
Recurrence
Signs and Symptoms
Cerebrovascular Accident
Hypoxia-Ischemia, Brain
Pathologic Processes
Aspirin
Clopidogrel
Brain Ischemia
Brain Infarction
Infarction




Additional relevant MeSH terms:
Antimetabolites
Disease Attributes
Antilipemic Agents
Nervous System Diseases
Hematologic Agents
Enzyme Inhibitors
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Molecular Mechanisms of Action
Pathological Conditions, Signs and Symptoms
Therapeutic Uses
Cardiovascular Diseases
Platelet Aggregation Inhibitors



ClinicalTrials.gov processed this record on December 14, 2007

Source: http://www.ndm.ox.ac.uk/ndmjr/researchunits/geratology/abuchan