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

Sponsor

Beijing Tiantan Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00979589

Collaborator

University of California, San Francisco (Other)

5,100

Enrollment

Location

Arms

Duration (Months)

170

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke Transient Ischemic Attack	Drug: Clopidogrel Drug: Placebo of clopidogrel and Asprin	Phase 3

Detailed Description

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

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

5100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

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 Start Date :

Dec 1, 2009

Actual Primary Completion Date :

Mar 1, 2012

Actual Study Completion Date :

Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Combination Clopidogrel and asprin	Drug: Clopidogrel 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. Other Names: Plavix
Placebo Comparator: Asprin and placebo	Drug: Placebo of clopidogrel and Asprin 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. Other Names: Acetylsalicylic acid

Arm

Intervention/Treatment

Active Comparator: Combination Clopidogrel and asprin

Drug: Clopidogrel

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.

Other Names:

Plavix

Placebo Comparator: Asprin and placebo

Drug: Placebo of clopidogrel and Asprin

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.

Other Names:

Acetylsalicylic acid

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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]
Modified Rankin Scale score changes (continuous) and dichotomized at percentage with score 0-2 vs. 3-6 at 3 month follow-up [3 months]
Further efficacy exploratory analysis:Impairment (changes in NIHSS scores at 3 month follow-up). [3 months]
Further efficacy exploratory analysis:Quality of Life (EuroQol EQ-5D scale) [3 months]
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]
Severe bleeding incidence (GUSTO definition), including fatal bleeding and symptomatic intracranial hemorrhage. [3 months]
Incidence symptomatic and asymptomatic intracranial hemorrhagic events at 3 months [3 months]
Intracranial hemorrhage [3 months]
Total mortality [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Tian Tan Hospital, Capital Medical University	Beijing		China	100050

Sponsors and Collaborators

Beijing Tiantan Hospital
University of California, San Francisco

Investigators

Principal Investigator: Yongjun NA Wang, M.D, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
Principal Investigator: S.Claiborne NA Johnston, M.D, Ph.D, Departments of Neurology, Epidemiology, University of California, San Francisco, USA