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

Обзор

The objective of this clinical trial is to evaluate the efficacy and safety of platelet aggregation function - guided precision anti - platelet therapy in patients with acute cerebral infarction. The main question it aims to answer is: among the cerebral infarction patients with possible clopidogrel resistance detected by platelet aggregation function tests, what is the efficacy and safety of using ticagrelor to replace the clopidogrel treatment regimen.

Вмешательства

• Препарат The ticagrelor
  Ticagrelor 90 mg should be administered as early as possible (within 12-24 hours after the loading dose). From Day 1 to Day 21 after enrollment: Patients shall receive dual antiplatelet therapy with oral ticagrelor 90 mg bid and aspirin 100 mg qd. From Day 22 to Day 90 after enrollment: Patients shall receive monotherapy with oral ticagrelor 90 mg bid.
• Препарат The Clopidogrel
  From the 1st to the 21st day, the patient should receive dual anti - platelet therapy with clopidogrel 75mg once a day (qd) combined with aspirin 100mg once a day (qd). From the 22nd to the 90th day, the patient should be given clopidogrel 75mg qd for anti - platelet treatment.

Первичные конечные точки

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

Вторичные конечные точки (6)

• Recurrent ischemic stroke [Срок оценки: On the 7th day, at 30 days, and within 1 year]
• New-onset vascular events [Срок оценки: On the 7th day, at 30 days, at 90 days and within 1 year.]
• Modified Rankin Scale (mRS) score [Срок оценки: at 30 days, 90 days, and 1 year]
• Recurrent stroke [Срок оценки: On the 7th day, the 30th day, the 90th day and within one year.]
• Worsening of nerve damage (an increase in the NIHSS score by ≥ 4 points compared to the baseline) [Срок оценки: At the 24th hour and on the 7th day]
• Quality of life at day 90 [assessed by the EuroQol - 5 dimension (EQ - 5D) questionnaire] [Срок оценки: at 90 days]

Критерии участия

Критерии включения

• Age ≥ 18 years old.
• 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.
• 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.)
• 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.
• Written informed consent signed by the patient or their legal representative.

Критерии исключения

• 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).
• Minor stroke/TIA induced by angioplasty or vascular surgery.
• 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.
• Having definite indications for anticoagulant therapy (suspected cardiogenic embolism, e.g., atrial fibrillation, known artificial heart valve, suspected endocarditis, etc.).
• 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.
• Use of antiplatelet agents other than aspirin and clopidogrel (e.g., ticagrelor, prasugrel) within 7 days.
• 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).
• 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.
• Leukopenia (< 2×10⁹/L) or thrombocytopenia (< 100×10⁹/L).
• Use of heparin or oral anticoagulants within 10 days prior to enrollment.
• 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).
• Women of childbearing age with a negative pregnancy test but who refuse to adopt effective contraceptive measures; pregnant or lactating women.
• Poor compliance, unable to cooperate with the requirements of the study.

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

• 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
• 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
• Wang Y, Chen W, Lin Y, Meng X, Chen G, Wang Z, Wu J, Wang D, Li J, Cao Y, Xu Y, Zhang G, Li X, Pan Y, Li H, Zhao X, Liu L, Lin J, Dong K, Jing J, Johnston SC, Wang D, Wang Y; PRINCE Protocol Steering Group. Ticagrelor plus aspirin versus clopidogrel plus aspirin for platelet reactivity in patients with minor stroke or transient ischaemic attack: open label, blinded endpoint, randomised controlled PMID 31171523
• Zhu HC, Li Y, Guan SY, Li J, Wang XZ, Jing QM, Wang ZL, Han YL. Efficacy and safety of individually tailored antiplatelet therapy in patients with acute coronary syndrome after coronary stenting: a single center, randomized, feasibility study. J Geriatr Cardiol. 2015 Jan;12(1):23-9. doi: 10.11909/j.issn.1671-5411.2015.01.003. PMID 25678901
• Cayla G, Cuisset T, Silvain J, Leclercq F, Manzo-Silberman S, Saint-Etienne C, Delarche N, Bellemain-Appaix A, Range G, El Mahmoud R, Carrie D, Belle L, Souteyrand G, Aubry P, Sabouret P, du Fretay XH, Beygui F, Bonnet JL, Lattuca B, Pouillot C, Varenne O, Boueri Z, Van Belle E, Henry P, Motreff P, Elhadad S, Salem JE, Abtan J, Rousseau H, Collet JP, Vicaut E, Montalescot G; ANTARCTIC investigator PMID 27581531
• Galli M, Benenati S, Capodanno D, Franchi F, Rollini F, D'Amario D, Porto I, Angiolillo DJ. Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis. Lancet. 2021 Apr 17;397(10283):1470-1483. doi: 10.1016/S0140-6736(21)00533-X. PMID 33865495
• Zheng YY, Wu TT, Yang Y, Hou XG, Gao Y, Chen Y, Yang YN, Li XM, Ma X, Ma YT, Xie X. Personalized antiplatelet therapy guided by a novel detection of platelet aggregation function in stable coronary artery disease patients undergoing percutaneous coronary intervention: a randomized controlled clinical trial. Eur Heart J Cardiovasc Pharmacother. 2020 Jul 1;6(4):211-221. doi: 10.1093/ehjcvp/pvz059. PMID 31603191
• 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

Идентификаторы

NCT: NCT06853535 · IITLX2025007

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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