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

This study has been completed.
Sponsor:
Collaborator:
University of California, San Francisco
Information provided by (Responsible Party):
yongjun wang, Ministry of Science and Technology of the People´s Republic of China
ClinicalTrials.gov Identifier:
NCT00979589
First received: September 17, 2009
Last updated: March 11, 2012
Last verified: March 2012
  Purpose

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 Intervention Phase
Stroke
Transient Ischemic Attack
Drug: Clopidogrel
Drug: Placebo of clopidogrel and Asprin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Ministry of Science and Technology of the People´s Republic of China:

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) [ Time Frame: 3 months ] [ Designated as safety issue: No ]

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. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Modified Rankin Scale score changes (continuous) and dichotomized at percentage with score 0-2 vs. 3-6 at 3 month follow-up [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Further efficacy exploratory analysis:Impairment (changes in NIHSS scores at 3 month follow-up). [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Further efficacy exploratory analysis:Quality of Life (EuroQol EQ-5D scale) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Severe bleeding incidence (GUSTO definition), including fatal bleeding and symptomatic intracranial hemorrhage. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Incidence symptomatic and asymptomatic intracranial hemorrhagic events at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Intracranial hemorrhage [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Total mortality [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Enrollment: 5100
Study Start Date: July 2008
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Acetylsalicylic acid

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

Ages Eligible for Study:   40 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00979589

Locations
China
Beijing Tian Tan Hospital, Capital Medical University
Beijing, China, 100050
Sponsors and Collaborators
yongjun wang
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
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: yongjun wang, Vice president of Beijing Tiantan Hospital, Ministry of Science and Technology of the People´s Republic of China
ClinicalTrials.gov Identifier: NCT00979589     History of Changes
Other Study ID Numbers: 2008ZX09312-008
Study First Received: September 17, 2009
Last Updated: March 11, 2012
Health Authority: The people's republic of China: The Ministry of Science and Technology

Keywords provided by Ministry of Science and Technology of the People´s Republic of China:
stroke
transient ischemic attack
acute treatment
acute non-disabling cerebrovascular event
clopidogrel
clopidogrel combined with ASA
recurrence of stroke and other vascular events

Additional relevant MeSH terms:
Stroke
Cerebral Infarction
Ischemic Attack, Transient
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Clopidogrel
Ticlopidine
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 22, 2014