Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II
Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II
The primary objective of this trial is to assess the effects of ticagrelor plus aspirin
 versus clopidogrel plus aspirin on reducing the 3-month risk of any stroke (both ischemic and
 hemorrhagic, primary outcome) when initiated within 24 hours of symptom onset in CYP2Y19 LOF
 alleles carriers with TIA or minor stroke.
According to the Global Burden of Disease(GBD) Study 2016, China bears the greatest lifetime
 risk of stroke from 25-year-age onward. Minor ischemic events, including minor stroke and
 TIA, were major parts of stroke manifestations. Events (CHANCE) has shown that 21-day dual
 antiplatelet therapy (clopidogrel and aspirin) compared to aspirin alone which initiated
 within 24 hours after symptoms onset would reduce 32% risk of stroke recurrence within 90
 day, but not in carriers of CYP2C19 loss-of-function (LOF) alleles. The primary purpose of
 this study is to compare ticagrelor plus aspirin with clopidogrel plus aspirin on reducing
 the 3-month risk of any stroke (both ischemic and hemorrhagic, primary outcome) when
 initiated within 24 hours of symptom onset in CYP2Y19 LOF alleles carriers with TIA or minor
 stroke.

 Both intent analysis (ITT) and compliance program set (PPS) were used for analysis.

 We will use Kaplan-Meier estimates of the cumulative risk of stroke (ischemic or hemorrhagic)
 event during maximum 90-day follow-up, with hazards ratios and 95% CI calculated using Cox
 proportional hazards methods and the log-rank test to evaluate the treatment effect. All
 statistics will be 2-sided with P<0.05 considered significant, accounting for interim
 analyses.

 All patients who received study drugs and with at least one safety follow-up record will be
 included in the safety population. The data for safety evaluation included adverse reactions
 observed during the trial and changes in laboratory data before and after treatment.
Inclusion Criteria

 1. 40 years or older than 40 years；

 2. Acute cerebral ischemic event due to：

 -  Acute non-disabling ischemic stroke (NIHSS≤3 at the time of randomization)or，

 -  TIA with moderate-to-high risk of stroke (ABCD2 score ≥ 4 at the time of
 randomization)；

 3. Can be treated with study drug within 24 hours of symptoms onset*(*Symptom onset is
 defined by the "last seen normal" principle)；

 4. CYP2C19 loss-of-function allele carriers；

 5. Informed consent signed.

 Exclusion Criteria

 1. Malformation, tumor, abscess or other major non-ischemic brain disease (e.g., multiple
 sclerosis) on baseline head CT or MRI.

 2. 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.

 3. Iatrogenic causes (angioplasty or surgery) of minor stroke or TIA.

 4. Preceding moderate or severe dependency (modified Rankin scale [mRS] score 3-5).

 5. Contraindication to clopidogrel, ticagrelor or aspirin

 -  Known allergy

 -  Severe renal (creatinine exceeding 1.5 times of the upper limit of normal range)
 or hepatic (ALT or AST > twice the upper limit of normal range) insufficiency

 -  Severe cardiac failure (NYHA level: III to IV)

 -  History of hemostatic disorder or systemic bleeding

 -  History of thrombocytopenia or neutropenia

 -  History of drug-induced hematologic disorder or hepatic dysfunction

 -  Low white blood cell (<2×109/L) or platelet count (<100×109/L)

 6. Hematocrit (HCT) <30%

 7. Clear indication for anticoagulation (presumed cardiac source of embolus, e.g., atrial
 fibrillation, prosthetic cardiac valves known or suspected endocarditis)

 8. History of intracranial hemorrhage or amyloid angiopathy

 9. History of aneurysm (including intracranial aneurysm and peripheral aneurysm)

 10. History of asthma or COPD (chronic obstructive pulmonary disease)

 11. High-risk for bradyarrhythmia (first-degree or second-degree AV block caused by sinus
 node disease, and brady-arrhythmic syncope without pacemaker)

 12. History of hyperuricemia nephropathy

 13. Anticipated requirement for long-term (>7 days) non-steroidal anti-inflammatory drugs
 (NSAIDs)

 14. Planned or likely revascularization (any angioplasty or vascular surgery) within the
 next 3 months

 15. Scheduled for surgery or interventional treatment requiring study drug cessation

 16. Severe non-cardiovascular comorbidity with life expectancy < 3 months

 17. Inability to understand and/or follow research procedures due to mental, cognitive, or
 emotional disorders

 18. Dual antiplatelet treatment (or more than two antiplatelet agents) in 72 hours before
 randomization

 19. Current treatment (last dose given within 10 days before randomization) with heparin
 therapy or oral anti coagulation

 20. Intravenous thrombolytic therapy (such as intravenous rtPA) or mechanical thrombectomy
 within 24 hours prior to randomization

 21. Gastrointestinal bleed within 3 months or major surgery within 30 days

 22. Diagnosis or suspicious diagnosis of acute coronary syndrome

 23. Participation in another clinical study with an experimental product during the last
 30 days

 24. Currently receiving an experimental drug or device

 25. Pregnant, currently trying to become pregnant, or of child-bearing potential and not
 using birth control