Clopidogrel in High-risk Patients With Acute Non-disabling Cerebrovascular Events

Condition(s) targeted: Stroke; Transient Ischemic Attack

Intervention: Clopidogrel (Drug); Placebo of clopidogrel and Asprin (Drug)

Phase: Phase 3

Status: Not yet recruiting

Sponsored by: Ministry of Science and Technology of the People´s Republic of China

Official(s) and/or principal investigator(s):
Yongjun Wang, M.D, Principal Investigator, Affiliation: Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
S.Claiborne Johnston, M.D, Ph.D, Principal Investigator, Affiliation: Departments of Neurology, Epidemiology, University of California, San Francisco, USA

Overall contact:
yilong Wang, M.D, Phone: 00861067013383, Email: yilong528@gmail.com

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.

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 High-risk Patients With Acute Non-disabling Cerebrovascular Event (TIA or Minor Stroke)

Study design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Percentage of patients with the 3-month new vascular events, defined as any event of the following: Any stroke (ischemic or hemorrhage)

Secondary outcome:

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.

Modified Rankin Scale score changes (continuous) and dichotomized at percentage with score 0-2 vs. 3-6 at 3 month follow-up

Further efficacy exploratory analysis:Impairment (changes in NIHSS scores at 3 month follow-up).

Further efficacy exploratory analysis:Cognitive function (changes in MoCA score will be calculated between baseline and at 3 month visit).

Further efficacy exploratory analysis:Quality of Life (EuroQol EQ-5D scale)

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

Severe bleeding incidence (GUSTO definition), including fatal bleeding and symptomatic intracranial hemorrhage.

Incidence symptomatic and asymptomatic intracranial hemorrhagic events at 3 months

Intracranial hemorrhage

Total mortality

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).

Minimum age: 40 Years. Maximum age: 90 Years. Gender(s): Both.

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

yilong Wang, M.D, Phone: 00861067013383, Email: yilong528@gmail.com

Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China

Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China

Tiantan clinical trial and research center for stroke

Related publications:

Liu M, Wu B, Wang WZ, Lee LM, Zhang SH, Kong LZ. Stroke in China: epidemiology, prevention, and management strategies. Lancet Neurol. 2007 May;6(5):456-64. Review.

Starting date: December 2009
Ending date: December 2011
Last updated: October 13, 2009