The purpose of this study is to assess the effects of a 3-month regimen of clopidogrel initiated with a loading dose (LD) of 300 mg followed by 75 mg/day during the first 21days versus a 3-month regimen of ASA 75 mg/day alone on reducing the 3-month risk of any stroke (both ischemic and hemorrhagic, primary outcome) when initiated within 24 hours of symptom onset in high-risk patients with TIA or minor stroke.
1. Adult subjects (male or female ≥ 40 years)
2. Acute non-disabling ischemic stroke (NIHSS≤3 at the time of randomization) that can be treated with study drug within 24 hours of symptoms onset. Symptom onset is defined by the "last see normal" principle.
3. TIA (Neurological deficit attributed to focal brain ischemia, with resolution of the deficit within 24 hours of symptom onset), that can be treated with study drug within 24 hours of symptoms onset and with moderate-to-high risk of stroke recurrence (ABCD2 score ≥ 4 at the time of randomization). Symptom onset is defined by the "last see normal" principle.
4. Informed consent signed
Primary Efficacy Endpoint:
Percentage of patients with the 3-month new vascular events, defined as any event of the following:Any stroke (ischemic or hemorrhage).
- Clopidogrel (Plavix®)Drug
Other Names: Plavix, Clodelib, Clovelen Intervention Desc: The first group will receive a 300mg loading dose (LD) of clopidogrel on the day of randomization, followed by 75 mg clopidogrel/day from Day 2 to 3 months. ASA will be given in a total dose ranging between 75 mg and 300 mg (open label) on the first day, followed by blinded 75 mg once /day from Day 2 to Day 21st. Between Day 21st and 3-month visits, ASA 75 mg will be replaced by a placebo of ASA 75 mg. ARM 1: Kind: Experimental Label: Combination Clopidogrel and asprin
- Placebo of clopidogrel and Asprin Drug
Other Names: Acetylsalicylic acid Intervention Desc: The second group will receive open label ASA in a total dose ranging between 75 mg and 300 mg on the first day, followed by blinded 75 mg once /day from Day 2 to 3 months. A placebo for clopidogrel will be given from the day of randomization until the 3-month visit. ARM 1: Kind: Experimental Label: Asprin and placebo
- Allocation: Randomized
- Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
- Purpose: Prevention
- Endpoint: Safety/Efficacy Study
- Intervention: Parallel Assignment
|Type||Measure||Time Frame||Safety Issue|
|Primary||Percentage of patients with the 3-month new vascular events, defined as any event of the following: Any stroke (ischemic or hemorrhage)||3 months||No|
|Secondary||Percentage of patients with the 3-month new clinical vascular events (ischemic stroke/ hemorrhagic stroke/ TIA/ MI/ vascular death) as a cluster and evaluated individually.||3 months||No|
|Secondary||Modified Rankin Scale score changes (continuous) and dichotomized at percentage with score 0-2 vs. 3-6 at 3 month follow-up||3 months||No|
|Secondary||Further efficacy exploratory analysis:Impairment (changes in NIHSS scores at 3 month follow-up).||3 months||No|
|Secondary||Further efficacy exploratory analysis:Quality of Life (EuroQol EQ-5D scale)||3 months||No|
|Secondary||Efficacy endpoint will also be analyzed stratified by etiological subtypes, by time randomization (< 12 hours vs. ≥ 12 hours), by qualifying event (TIA vs. minor stroke), and by age||3 months||No|
|Secondary||Severe bleeding incidence (GUSTO definition), including fatal bleeding and symptomatic intracranial hemorrhage.||3 months||Yes|
|Secondary||Incidence symptomatic and asymptomatic intracranial hemorrhagic events at 3 months||3 months||Yes|
|Secondary||Intracranial hemorrhage||3 months||Yes|
|Secondary||Total mortality||3 months||Yes|