Platelet Aggregation Function-Guided De-Escalation Antiplatelet Therapy in Patients With Acute Ischemic Stroke

Обзор

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.

Вмешательства

• Препарат Clopidogrel
  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.
• Препарат Aspirin
  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.

Первичные конечные точки

• Recurrent stroke (including ischemic and hemorrhagic stroke) within 90 days [Срок оценки: within 90 days]

Вторичные конечные точки (6)

• New stroke at prespecified follow-up visits [Срок оценки: At Day 7 or hospital discharge, Day 30 and 1 year after randomization]
• New vascular events [Срок оценки: At Day 7 or hospital discharge, Day 30, Day 90, and 1 year after randomization]
• Modified Rankin Scale score [Срок оценки: At Day 30, Day 90, 1 year, and 2 years after randomization]
• New ischemic stroke [Срок оценки: 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) [Срок оценки: 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] [Срок оценки: At Day 90 after randomization]

Критерии участия

Критерии включения

• 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.

\-

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

• Sichuan Provincial People's Hospital — Чэнду

Публикации

• Savcic M, Hauert J, Bachmann F, Wyld PJ, Geudelin B, Cariou R. Clopidogrel loading dose regimens: kinetic profile of pharmacodynamic response in healthy subjects. Semin Thromb Hemost. 1999;25 Suppl 2:15-9. PMID 10440417
• Ma L, Chen W, Pan Y, Yan H, Li H, Meng X, Wang Y, Wang Y. Comparison of VerifyNow, thromboelastography, and PL-12 in patients with minor ischemic stroke or transient ischemic attack. Aging (Albany NY). 2021 Mar 3;13(6):8396-8407. doi: 10.18632/aging.202650. Epub 2021 Mar 3. PMID 33686963
• Yang Y, Chen W, Pan Y, Yan H, Meng X, Liu L, Wang Y, Wang Y. Ticagrelor Is Superior to Clopidogrel in Inhibiting Platelet Reactivity in Patients With Minor Stroke or TIA. Front Neurol. 2020 Jun 10;11:534. doi: 10.3389/fneur.2020.00534. eCollection 2020. PMID 32587571
• Tarantini G, Honton B, Paradies V, Lemesle G, Range G, Godin M, Mangin L, Cuisset T, Ruiz-Nodar JM, Brugaletta S, Lhermusier T, Piot C, De Poli F, Macia JC, Motreff P, Madera-Cambero M, Beygui F, Riccini P, Ranc S, Oreglia JA, Vaquerizo B, Poezevara Y, Bouchez D, Smits PC, Cayla G; TARGET-FIRST Investigators. Early Discontinuation of Aspirin after PCI in Low-Risk Acute Myocardial Infarction. N Eng PMID 40888726
• Tarantini G, Smits PC, Lhermusier T, Honton B, Range G, Piot C, Lemesle G, Ruiz Nodar JM, Godin M, Madera Cambero M, Motreff P, Cuisset T, Bouchez D, Poezevara Y, Cayla G. A prospective study comparing short versus standard dual antiplatelet therapy in patients with acute myocardial infarction: design and rationale of the TARGET-FIRST trial. EuroIntervention. 2023 Jun 19;19(3):240-247. doi: 10.424 PMID 36999409
• Tavenier AH, Mehran R, Chiarito M, Cao D, Pivato CA, Nicolas J, Beerkens F, Nardin M, Sartori S, Baber U, Angiolillo DJ, Capodanno D, Valgimigli M, Hermanides RS, van 't Hof AWJ, Ten Berg JM, Chang K, Kini AS, Sharma SK, Dangas G. Guided and unguided de-escalation from potent P2Y12 inhibitors among patients with acute coronary syndrome: a meta-analysis. Eur Heart J Cardiovasc Pharmacother. 2022 Au PMID 34459481
• Kwon TJ, Tantry US, Park Y, Choi YM, Ahn JH, Kim KH, Koh JS, Park JR, Hwang SJ, Kwak CH, Hwang JY, Gurbel PA, Smith SC Jr, Jeong YH. Influence of platelet reactivity on BARC classification in East Asian patients undergoing percutaneous coronary intervention. Results of the ACCEL-BLEED study. Thromb Haemost. 2016 May 2;115(5):979-92. doi: 10.1160/TH15-05-0366. Epub 2016 Jan 21. PMID 26790469
• Valgimigli M, Choi KH, Giacoppo D, Gragnano F, Kimura T, Watanabe H, Kim HS, Kang J, Park KW, Pettersen AA, Woodward M, Bhatt DL, Calabro P, Angiolillo DJ, Mehran R, Song YB, Hahn JY. Clopidogrel versus aspirin for secondary prevention of coronary artery disease: a systematic review and individual patient data meta-analysis. Lancet. 2025 Sep 13;406(10508):1091-1102. doi: 10.1016/S0140-6736(25)0156 PMID 40902613

Идентификаторы

NCT: NCT07644234 · IITLX2026028

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗