CHANCE Trial: Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack
In patients with high-risk TIA or minor ischemic stroke presenting within 24 hours, does dual antiplatelet therapy with clopidogrel plus aspirin reduce recurrent stroke at 90 days compared with aspirin monotherapy?
Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369(1):11-19. · doi:10.1056/NEJMoa1215340 · 5,170 patients
Population
Included
- Age 40 years or older
- Minor ischemic stroke (NIHSS 0 to 3) or high-risk TIA (ABCD2 score 4 or higher)
- Randomization within 24 hours of symptom onset
- No clear indication for anticoagulation (no atrial fibrillation, no prosthetic valve)
- Independent at baseline
Eligible patients
- Age 40 years or older
- Diagnosis of an acute minor ischemic stroke or TIA
- Acute minor stroke defined by a score of 3 or less on the NIHSS (range 0 to 42) at the time of randomization
- TIA defined as focal brain ischemia with resolution of symptoms within 24 hours after onset plus a moderate-to-high risk of stroke recurrence (ABCD2 score of 4 or higher at randomization)
- Ability to start the study drug within 24 hours after symptom onset
Excluded
- Hemorrhagic stroke on baseline imaging
- Severe stroke (NIHSS 4 or higher)
- Low-risk TIA (ABCD2 below 4)
- Clear indication for anticoagulation (atrial fibrillation, valvular disease)
- Recent major surgery or GI bleeding within 3 months
- Contraindication to clopidogrel or aspirin
Hemorrhage / non-ischemic
- Hemorrhage or other conditions (vascular malformation, tumor, abscess, or other major nonischemic brain disease) on baseline CT or MRI
- Isolated sensory symptoms, isolated visual changes, or isolated dizziness or vertigo without evidence of acute infarction on baseline imaging
Baseline disability / severity
- A modified Rankin scale score of more than 2 immediately before the index event
- An NIHSS score of 4 or more at randomization
Anticoagulation / bleeding
- A clear indication for anticoagulation (presumed cardiac source of embolus, such as atrial fibrillation or prosthetic valve)
- Contraindication to clopidogrel or aspirin
- History of intracranial hemorrhage
- Anticipated long-term need for nonstudy antiplatelet drugs or NSAIDs affecting platelet function
- Heparin or oral anticoagulation within 10 days before randomization
- Gastrointestinal bleeding or major surgery within the previous 3 months
Procedures / prognosis
- Planned or probable revascularization within 3 months
- Planned surgery or intervention requiring cessation of the study drug
- TIA or minor stroke caused by angiography or surgery
- Severe noncardiovascular condition with life expectancy less than 3 months
- Women of childbearing age without reliable contraception and without a negative pregnancy test
- Receiving other investigational drugs or devices
Source: Wang Y et al., N Engl J Med 2013· Retrieved 2026-06-09
Primary Outcome
Small absolute difference — interpret with caution
Stroke-free at 90 Days
Study Arms
- Agent
- Clopidogrel plus aspirin
- Dose
- Clopidogrel 300 mg loading on day 1, then 75 mg daily on days 2 to 90; aspirin 75 mg daily on days 2 to 21, then placebo aspirin on days 22 to 90 (open-label aspirin 75 to 300 mg on day 1)
- Route
- Oral
- Frequency
- Once daily
- Duration
- Clopidogrel days 1 to 90; aspirin (active) days 1 to 21, then clopidogrel alone to day 90
- Co-interventions
- Open-label aspirin on day 1 (75 to 300 mg) in both groups at physician discretion
Double-blind, double-dummy design
- Agent
- Aspirin plus placebo clopidogrel
- Dose
- Placebo clopidogrel days 1 to 90; aspirin 75 mg daily days 2 to 90 (open-label aspirin 75 to 300 mg on day 1)
- Route
- Oral
- Frequency
- Once daily
- Duration
- Aspirin days 1 to 90
- Co-interventions
- Open-label aspirin on day 1 (75 to 300 mg) in both groups at physician discretion
Placebo clopidogrel days 1 to 90
Safety
Moderate-to-severe hemorrhage at 90 days
0.3%
0.3%
Moderate-to-severe hemorrhage (GUSTO criteria): 0.3% DAPT vs 0.3% aspirin (P=0.73). No significant increase in severe bleeding with short-term dual antiplatelet therapy. Hemorrhagic stroke was 0.3% in both groups (P=0.98). Source: Wang Y et al., NEJM 2013, Table 2.
Trial Design
Type
- Randomized double-blind placebo-controlled trial
- Conducted in China (114 centers)
- 1:1 allocation (DAPT vs. Aspirin)
- Double-dummy design to maintain blinding
Timeline
Enrolled 2009-2012
N
5,170
Enrollment
5,170 patients at 114 centers in China. Enrolled 2009 to 2012.
ClinicalTrials.gov
NCT00979589Bedside Pearl
CHANCE: start clopidogrel 300mg load + aspirin within 24 hours of minor stroke or high-risk TIA. Run dual therapy for 21 days, then switch to monotherapy. NNT=29, major hemorrhage 0.3% in both groups. Do not extend to 90 days without considering POINT bleeding data.