Aspirin was reported to induce hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency on some occasions, while still widely uesd for stroke prevention. The SAST trial is designed to evaluate the safety and efficacy of aspirin in patients this enzyme disorder.The primary purpose of the trial is to evaluate the hemolytic effects of a 3-month regimen of aspirin 100mg/d versus a 3-month regimen of clopidogrel 75mg/d.

This SAST trial is a prospective, multicenter, randomized, double-blind trial.440 acute ischemic stroke (AIS) patients with G6PD deficiency will be randomized to receive a 3-month regimen of aspirin 100mg/d or clopidogrel 75mg/d. The primary end point is the proportion of protocol-defined hemolysis at 90 days. Protocol-defined hemolysis is defined as one or more of the following conditions: a) Hemoglobin level declined ≥2.5 g/dL from baseline, meanwhile ruling out bleeding events. b) Hemoglobin level declined ≥25% from baseline, meanwhile ruling out bleeding events. c) Clinically relevant hemolytic events, could manifested as fatigue, back pain, anemia, dark urine and jaundice. The study consists of five visits including the day of randomization, day 4, day10±3days, day27±3days, day90±7days.

Inclusion Criteria:

1. Age≥40 years(no upper limit)
2. Acute ischemic stroke within 14 days of symptoms onset;
3. Glucose-6-phosphate dehydrogenase deficiency screened in G6PD enzyme activity
4. Had not received aspirin 7 days prior to randomization
5. Informed consent signed

Exclusion Criteria:

1. Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other non-ischemic brain disease, base on head CT or MRI
2. Concomitant infections at the time of randomization
3. mRS>2 prior to the presenting stroke
4. Hemoglobin<10 g/dL prior to randomization
5. Received intravenous thrombolytic therapy or neurointervention treatment before randomization
6. Clear indication for anticoagulation (presumed cardioembolism, eg, atrial fibrillation, prosthetic cardiac valves or suspected endocarditis)
7. Clear indication for dual antiplatelet therapy (eg, minor stroke in 24h (NIHSS ≤3) or endovascular therapy for the indexed event)
8. Anticipated concomitant antiplatelets other than aspirin or clopidogrel (eg, GPIIb/IIIa inhibitors, ticlopidine, prasugrel, dipyridamole, ozagrel, cilostazol, ticagrelor) and other antithrombotic agents with antiplatelet effects, including traditional/herbal medicine agents.
9. Anticipated concomitant therapy with long-term (>7 days) NSAIDs affecting platelet function
10. Contraindication to clopidogrel or aspirin (1)Known allergic reactions (2)Severe hepatic or renal dysfunction (Severe hepatic dysfunction is defined as serum ALT or AST >2 times the upper limit of the normal group；Severe renal dysfunction is defined as serum creatinine > 1.5 times the upper limit of the normal group) (3)Severe cardiac failure（NYHA class Ⅲ or Ⅳ) (4)Asthma (5)Any history of Hemostatic disorder or systemic bleeding (6)Any history of thrombocytopenia or neutropenia (7)Any history of drug-induced hematologic or hepatic insufficiency (8)Low white blood cell (<2×10^9/L) or platelet count (<100×10^9/L)
11. Any history of thalassemia, autoimmune hemolytic disease, aplastic anemia or other severe hematologic diseases
12. Anticipated concomitant therapy with other contraindicated drugs for G6PD deficiency
13. Severe dysphagia to unable swallow the drugs
14. Concomitant infections and need for antimicrobial therapy
15. Intracranial hemorrhage or gastrointestinal bleed within 3 months, or major surgery within 30 days
16. Stomach tumor or any other malignant tumor
17. Planed surgery or interventional treatment that may affect the study procedure
18. Severe non-cardiovascular comorbidity with life expectancy <3 m
19. Female who is pregnant or lactating
20. Currently receiving an investigational drug or device
21. Inability to understand and/or comply with study procedures due to psychosis, cognition impairment or emotion disturbance.