Ischemic Stroke, Transient Ischemic Attack
Conditions
Keywords
Antiplatelet de-escalation, Ischemic Stroke, Platelet function tests, RCT
Brief summary
This multicenter, prospective, open-label, randomized controlled trial will evaluate whether platelet aggregation function-guided de-escalation of antiplatelet therapy is non-inferior in efficacy and superior in safety compared with standard dual antiplatelet therapy in patients with acute minor ischemic stroke or high-risk transient ischemic attack who are sensitive to clopidogrel. Participants who present within 48 hours of symptom onset and meet the eligibility criteria will receive loading doses of clopidogrel and aspirin, followed by platelet aggregation function testing. Eligible clopidogrel-sensitive participants will be randomized to receive either 7 days of dual antiplatelet therapy followed by clopidogrel monotherapy or standard 21-day dual antiplatelet therapy followed by single antiplatelet therapy. The primary efficacy outcome is new stroke within 90 days after randomization.
Interventions
DRUGClopidogrel
Clopidogrel will be administered according to the assigned antiplatelet strategy. Participants receive a loading dose during screening and then clopidogrel 75 mg orally once daily during the assigned treatment period.
DRUGAspirin
Aspirin will be administered according to the assigned antiplatelet strategy. Participants receive aspirin during screening and then aspirin 100 mg orally once daily during the assigned treatment period.
Sponsors
Sichuan Provincial People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1.Age 18 years or older. 2.Diagnosis of acute non-disabling ischemic stroke or transient ischemic attack according to World Health Organization criteria, meeting one of the following definitions: acute non-disabling ischemic stroke, defined as a National Institutes of Health Stroke Scale score of 5 or lower at enrollment; or high-risk transient ischemic attack, defined as an ABCD2 score of 4 or higher. 3.Symptom onset within 48 hours. Onset time is defined as the interval from the last time the participant was known to be well to the time of combined administration of clopidogrel 300 mg and aspirin 100 mg. 4.MARADP \<35% measured 5 to 20 hours after combined antiplatelet treatment with clopidogrel 300 mg and aspirin 100 mg within 48 hours of symptom onset. 5.Planned treatment with aspirin plus clopidogrel or clopidogrel monotherapy for antiplatelet therapy. 6.Written informed consent provided by the participant or a legally authorized representative.
Exclusion criteria
1.Imaging evidence of hemorrhagic stroke, hemorrhagic transformation, or another pathological brain disorder, such as vascular malformation, tumor, abscess, or another common non-ischemic brain disease such as multiple sclerosis. 2.Minor stroke or transient ischemic attack caused by angioplasty or vascular surgery. 3.Atrial fibrillation indicated by standard electrocardiography or typical physical signs of atrial fibrillation, including absolutely irregular rhythm, variable intensity of the first heart sound, or pulse deficit. 4.A clear indication for anticoagulation, including suspected cardioembolism such as atrial fibrillation, known artificial heart valve, or suspected endocarditis. 5.Intravenous thrombolysis, intra-arterial thrombolysis, mechanical thrombectomy, or any revascularization procedure performed after the index event or planned within 90 days. 6.Use of antiplatelet agents other than aspirin or clopidogrel within 7 days before enrollment, such as ticagrelor or prasugrel. 7.History of gastrointestinal bleeding, intracranial hemorrhage, recent major bleeding or blood transfusion, excluding minor hemoptysis or minor abnormal vaginal bleeding, or other bleeding disorder caused by coagulation dysfunction, such as purpura. 8.Contraindication or intolerance to clopidogrel or aspirin, including known allergy; severe hepatic insufficiency or renal insufficiency; severe heart failure; coagulation disorder or history of systemic bleeding; history of thrombocytopenia or neutropenia; or history of drug-induced hematologic disease or hepatic dysfunction. 9.Leukopenia, defined as white blood cell count \<2 x 10\^9/L, or thrombocytopenia, defined as platelet count \<100 x 10\^9/L. 10.Use of heparin or oral anticoagulants within 10 days before enrollment. 11.Severe cardiac, pulmonary, hepatic, or renal dysfunction, or severe comorbid disease such as tumor, chronic airflow disease, severe dementia, or severe heart failure. 12.Female participants of childbearing potential with a negative pregnancy test who refuse to use effective contraception, or women who are pregnant or breastfeeding. 13.Poor compliance or inability to complete study requirements. \-
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Recurrent stroke (including ischemic and hemorrhagic stroke) within 90 days | within 90 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| New stroke at prespecified follow-up visits | At Day 7 or hospital discharge, Day 30 and 1 year after randomization | — |
| New vascular events | At Day 7 or hospital discharge, Day 30, Day 90, and 1 year after randomization | Including cardiovascular and cerebrovascular strokes, myocardial infarctions, and vascular deaths. |
| Modified Rankin Scale score | At Day 30, Day 90, 1 year, and 2 years after randomization | The score range of the scale is from 0 to 6. The higher the score, the worse the outcome. |
| New ischemic stroke | At Day 7 or hospital discharge, Day 30, Day 90, and 1 year after randomization | — |
| Worsening of nerve damage (an increase in the NIHSS score by ≥ 4 points compared to the baseline) | At 24 hours and at Day 7 or hospital discharge after randomization | — |
| Quality of life at day 90 [assessed by the EuroQol - 5 dimension (EQ - 5D) questionnaire] | At Day 90 after randomization | It is usually represented by a value between 0 and 1, where 1 represents perfect health, 0 represents death, and the intermediate values reflect different degrees of health status. |
Countries
China
Contacts
CONTACTJie Yang Deputy Director of the Department of Neurology
Outcome results
None listed