Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II

• Status: Active, not recruiting
• Trial end date: 2022-03-23
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Beijing Tiantan Hospital; Peking University Third Hospital
• Collaborators: Beijing Tiantan Hospital; Ministry of Science and Technology of the People´s Republic of China
• Treatments: Aspirin; Clopidogrel; Ticagrelor

Criteria

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