Clinical trial NCT00979589: Clopidogrel in High-risk Patients With Acute Non-disabling Cerebrovascular Events
Official title: Randomized,Double-blind Trial Comparing the Effects of a 3-month Clopidogrel Regimen,Combined With ASA During the First 21days,Versus ASA Alone for the Acute Treatment of TIA or Minor Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Stroke
Transient Ischemic Attack
Keywords: stroke
transient ischemic attack
acute treatment
acute non-disabling cerebrovascular event
clopidogrel
clopidogrel combined with ASA
recurrence of stroke and other vascular events
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
Collaborators: name: University of California, San Francisco
First posted: 2009-09-18
Enrollment: 5100
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: Inclusion criteria:

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).

Eligibility criteria: Inclusion criteria:

* Adult subjects (male or female≥40 years)
* 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
* 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
* Informed consent signed

Exclusion Criteria:

* Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other major non-ischemic brain disease (e.g., multiple sclerosis) on baseline head CT or MRI
* Isolated or pure sensory symptoms (e.g., numbness), isolated visual changes, or isolated dizziness/vertigo without evidence of acute infarction on baseline head CT or MRI
* Modified Rankin Scale Score\>2 at randomization (pre-morbid historical assessment)
* NIH Stroke Score≥4 at randomization
* Clear indication for anticoagulation(presumed cardiac source of embolus, e.g., atrial fibrillation, prosthetic cardiac valves known or suspected endocarditis)
* Contraindication to clopidogrel or ASA
* Known allergy
* Severe renal or hepatic insufficiency
* Severe cardiac failure, asthma
* Hemostatic disorder or systemic bleeding
* History of hemostatic disorder or systemic bleeding
* History of thrombocytopenia or neutropenia
* History of drug-induced hematologic or hepatic abnormalities
* Low white blood cell (\<2 x109/l) or platelet count (\<100 x109/l)
* Use of thrombolysis within 24 hours prior to randomization
* History of intracranial hemorrhage
* Anticipated requirement for long-term non-study antiplatelet drugs, or NSAIDs affecting platelet function
* Current treatment (last dose given within 10 days before randomization) with heparin therapy or oral anti coagulation
* Gastrointestinal bleed or major surgery within 3 months
* Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months (if clinically indicated, vascular imaging should be performed prior to randomization whenever possible)
* Scheduled for surgery or interventional treatment requiring study drug cessation
* Qualifying TIA or minor stroke induced by angiography or surgery
* Severe non-cardiovascular comorbidity with life expectancy \< 3 months
* Women of childbearing age not practicing reliable contraception who do not have a documented negative pregnancy test
* Currently receiving an investigational drug or device

Primary outcomes:
measure: Percentage of patients with the 3-month new vascular events, defined as any event of the following: Any stroke (ischemic or hemorrhage)
timeFrame: 3 months
Secondary outcomes:
measure: 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.
timeFrame: 3 months
measure: Modified Rankin Scale score changes (continuous) and dichotomized at percentage with score 0-2 vs. 3-6 at 3 month follow-up
timeFrame: 3 months
measure: Further efficacy exploratory analysis:Impairment (changes in NIHSS scores at 3 month follow-up).
timeFrame: 3 months
measure: Further efficacy exploratory analysis:Quality of Life (EuroQol EQ-5D scale)
timeFrame: 3 months
measure: 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
timeFrame: 3 months
measure: Severe bleeding incidence (GUSTO definition), including fatal bleeding and symptomatic intracranial hemorrhage.
timeFrame: 3 months
measure: Incidence symptomatic and asymptomatic intracranial hemorrhagic events at 3 months
timeFrame: 3 months
measure: Intracranial hemorrhage
timeFrame: 3 months
measure: Total mortality
timeFrame: 3 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tian Tan Hospital, Capital Medical University
Study officials:
affiliation: Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
name: Yongjun NA Wang, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Departments of Neurology, Epidemiology, University of California, San Francisco, USA
name: S.Claiborne NA Johnston, M.D, Ph.D
role: PRINCIPAL_INVESTIGATOR
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