Using platelet aggregation tests to guide antiplatelet treatment in acute ischemic stroke

Precision Antiplatelet Therapy Guided by Platelet Aggregation Function in Patients With Acute Ischemic STROKE

This trial will test whether switching adults with acute ischemic stroke or high-risk TIA who show clopidogrel resistance on platelet testing to ticagrelor reduces repeat strokes and is safe.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 5138 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sichuan Provincial People's Hospital (Academic / other)
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT06853535 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional trial enrolls adults with non-disabling acute ischemic stroke (NIHSS ≤5) or high-risk TIA (ABCD2 ≥4) within 48 hours of symptom onset who receive a clopidogrel 300 mg plus aspirin 100 mg loading dose. Platelet aggregation (MARADP) is measured 5–20 hours after loading, and patients with MARADP ≥35%—indicating possible clopidogrel resistance—are assigned to ticagrelor instead of clopidogrel to compare outcomes. The trial tracks recurrent ischemic events and safety outcomes, including bleeding, over the follow-up period. The goal is to determine whether platelet-function-guided switching to ticagrelor improves prevention of recurrent stroke without unacceptable safety risks.

Who should consider this trial

Good fit: Adults aged 18 or older with acute non-disabling ischemic stroke (NIHSS ≤5) or high-risk TIA (ABCD2 ≥4) within 48 hours who show MARADP ≥35% after a clopidogrel-plus-aspirin loading dose and provide informed consent are ideal candidates.

Not a fit: Patients with hemorrhagic stroke, hemorrhagic transformation on imaging, those beyond the 48-hour enrollment window, or patients who are not clopidogrel-resistant are unlikely to benefit from this platelet-guided ticagrelor switch.

Why it matters

Potential benefit: If successful, this approach could reduce recurrent stroke risk in patients who do not respond well to clopidogrel by offering a more effective antiplatelet option.

How similar studies have performed: Related research—most notably CHANCE-2—has shown that ticagrelor plus aspirin reduced recurrent stroke versus clopidogrel plus aspirin in patients with CYP2C19 loss-of-function alleles, while platelet-function-guided switching has shown mixed but promising results in smaller studies.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years old.
2. Patients diagnosed with acute non-disabling ischaemic stroke or transient ischaemic attack (TIA) with moderate to high stroke risk in accordance with the WHO diagnostic criteria, defined as follows:

   * Acute non-disabling ischaemic stroke: NIHSS score ≤ 5 at enrollment;
   * TIA with moderate to high stroke risk: ABCD₂ score ≥ 4.
3. Time from symptom onset ≤ 48 hours. (Definition of symptom onset time: the interval from the last time the patient was observed in a normal state to the time of co-administration of clopidogrel 300 mg and aspirin 100 mg.)
4. MARADP ≥ 35% measured at 5-20 hours after the patient received antiplatelet therapy with co-administration of clopidogrel 300 mg and aspirin 100 mg within 48 hours of symptom onset.
5. Written informed consent signed by the patient or their legal representative.

Exclusion Criteria:

1. Imaging examinations suggestive of hemorrhagic stroke, hemorrhagic transformation, or other pathological cerebral disorders, such as vascular malformation, tumor, abscess, or other common non-ischemic cerebral diseases (e.g., multiple sclerosis).
2. Minor stroke/TIA induced by angioplasty or vascular surgery.
3. Routine electrocardiogram (ECG) suggestive of atrial fibrillation (AF), or physical examination findings of typical AF signs including completely irregular cardiac rhythm, variable intensity of the first heart sound, and pulse deficit.
4. Having definite indications for anticoagulant therapy (suspected cardiogenic embolism, e.g., atrial fibrillation, known artificial heart valve, suspected endocarditis, etc.).
5. Patients who have received intravenous thrombolysis, intra-arterial thrombolysis, mechanical thrombectomy, or any revascularization surgery after the current onset, or plan to receive such procedures within 90 days.
6. Use of antiplatelet agents other than aspirin and clopidogrel (e.g., ticagrelor, prasugrel) within 7 days.
7. History of gastrointestinal bleeding, intracranial hemorrhage, massive hemorrhage or blood transfusion in the recent period (excluding mild hemoptysis and mild abnormal vaginal bleeding), or history of other hemorrhagic diseases caused by coagulation dysfunction (e.g., purpura).
8. Having contraindications to or intolerance of clopidogrel, ticagrelor, or aspirin, including:

   * Known history of hypersensitivity;
   * Severe hepatic or renal insufficiency (definition of severe hepatic insufficiency: ALT \> 2× upper limit of normal \[ULN\] or AST \> 2× ULN; definition of severe renal insufficiency: creatinine \> 1.5× ULN);
   * Severe heart failure (NYHA Class Ⅲ or Ⅳ);
   * Coagulation disorders or history of systemic hemorrhage;
   * History of previous thrombocytopenia or neutropenia;
   * History of previous drug-induced hematological diseases or hepatic dysfunction.
9. Leukopenia (\< 2×10⁹/L) or thrombocytopenia (\< 100×10⁹/L).
10. Use of heparin or oral anticoagulants within 10 days prior to enrollment.
11. Patients with severe cardiac, pulmonary, hepatic, or renal insufficiency, and those with severe comorbidities (e.g., malignancy, chronic airflow limitation, severe dementia, severe heart failure).
12. Women of childbearing age with a negative pregnancy test but who refuse to adopt effective contraceptive measures; pregnant or lactating women.
13. Poor compliance, unable to cooperate with the requirements of the study.

Where this trial is running

Chengdu, Sichuan

• Sichuan Provincial People's Hospital — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Study coordinator: Jie Yang Deputy Director of the Department of Neurology

Conditions Acute Ischemic Stroke; Clopidogrel Resistance