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Clopidogrel in High-risk Patients With Acute Non-disabling Cerebrovascular Events (CHANCE)
This study is currently recruiting participants.
Verified by Ministry of Science and Technology of the People´s Republic of China, January 2010
First Received: September 17, 2009   Last Updated: January 20, 2010   History of Changes
Sponsor: Ministry of Science and Technology of the People´s Republic of China
Collaborator: University of California, San Francisco
Information provided by: Ministry of Science and Technology of the People´s Republic of China
ClinicalTrials.gov Identifier: NCT00979589
  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 III

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

Estimated Enrollment: 5100
Study Start Date: July 2008
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Combination Clopidogrel and asprin: Active Comparator 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.
Asprin and placebo: Placebo Comparator 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.

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00979589

Contacts
Contact: yilong Wang, M.D 00861067013383 yilong528@gmail.com
Contact: xia Meng, M.D 00861067096699 mengxia45@163.com

Locations
China
Beijing Tian Tan Hospital, Capital Medical University Recruiting
Beijing, China, 100050
Contact: Yilong Wang, M.D     00861067013383     yilong528@gmail.com    
Contact: Xia Meng, M.D     00861067093383     mengxia45@163.com    
Principal Investigator: Yongjun Wang, M.D            
Principal Investigator: Claiborne Johnston, M.D, Ph.D            
Sponsors and Collaborators
Ministry of Science and Technology of the People´s Republic of China
University of California, San Francisco
Investigators
Principal Investigator: Yongjun Wang, M.D Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
Principal Investigator: S.Claiborne Johnston, M.D, Ph.D Departments of Neurology, Epidemiology, University of California, San Francisco, USA
  More Information

Additional Information:
Publications:
Responsible Party: Beijing Tian Tan Hospital, Capital Medical University, China ( Yongjun Wang )
Study ID Numbers: 2008ZX09312-008
Study First Received: September 17, 2009
Last Updated: January 20, 2010
ClinicalTrials.gov Identifier: NCT00979589     History of Changes
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:
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Cerebral Infarction
Hematologic Agents
Physiological Effects of Drugs
Fibrinolytic Agents
Brain Diseases
Cerebrovascular Disorders
Fibrin Modulating Agents
Aspirin
Sensory System Agents
Therapeutic Uses
Brain Ischemia
Cardiovascular Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Ischemic Attack, Transient
Ticlopidine
Cyclooxygenase Inhibitors
Nervous System Diseases
Stroke
Vascular Diseases
Central Nervous System Diseases
Enzyme Inhibitors
Cardiovascular Agents
Pharmacologic Actions
Analgesics, Non-Narcotic
Clopidogrel
Platelet Aggregation Inhibitors
Brain Infarction

ClinicalTrials.gov processed this record on February 08, 2010