Comparison of Clopidogrel-based Antiplatelet Therapy Versus Warfarin As Secondary Prevention Strategy for AntiPhospholipid Syndrome-related STROKE

Официальное название

Comparison of Clopidogrel-based Antiplatelet Therapy Versus Warfarin As Secondary Prevention Strategy for AntiPhospholipid Syndrome-related STROKE (APS-STROKE)

Обзор

Antiphospholipid syndrome (APS) has a close association with ischemic stroke; however, the optimal treatment strategy for APS-related stroke has yet to be established. The clinical guidelines suggest using warfarin for APS-related stroke, but these suggestions are largely based on retrospective studies from the 1990s and expert opinion, rather than high-quality clinical trials. Moreover, the evidence on the role of antiplatelet drugs other than aspirin (e.g., clopidogrel) in APS-related stroke is particularly limited. Considering the relatively young age of patients with APS and the high clinical burden of using warfarin, it is necessary to verify whether warfarin is essential. Thus, the investigators aim to compare clopidogrel-based antiplatelet therapy and warfarin as a secondary preventive medication for patients with APS-related stroke. APS-STROKE is an exploratory, multicenter, prospective, randomized, open, blinded-endpoint clinical trial. Adult patients with definite APS who have a history of ischemic stroke will be included. Patients with high-risk APS (triple positivity or persistently high titers of anti-cardiolipin or anti-β2-glycoprotein I antibodies), systemic lupus erythematous, or indications for continued antiplatelet or anticoagulant therapy will be excluded. Eligible patients will be 1:1 randomized to receive clopidogrel-based antiplatelet therapy or warfarin. Patients assigned to the clopidogrel-based antiplatelet therapy group will be permitted to use additional antiplatelet drugs other than clopidogrel at the investigator's discretion. The primary outcome is a composite of any death, major adverse cardiovascular events, systemic thromboembolic events, and major bleeding during a follow-up period of at least 4 years. This study would provide valuable information for determining the optimal secondary prevention strategy for APS-related stroke.

Вмешательства

• Препарат Antiplatelet Drug
  Clopidogrel ± other antiplatelet drug
• Препарат Warfarin
  Warfarin (target prothrombin time-international normalized ratio 2.0-3.0)

Первичные конечные точки

• Composite endpoint [Срок оценки: 4 years]

Вторичные конечные точки (8)

• MACE [Срок оценки: 4 years]
• Ischemic stroke [Срок оценки: 4 years]
• Any bleeding [Срок оценки: 4 years]
• Major bleeding [Срок оценки: 4 years]
• Intracranial bleeding [Срок оценки: 4 years]
• Clinically relevant non-major bleeding [Срок оценки: 4 years]
• Any death [Срок оценки: 4 years]
• Thrombosis-related death [Срок оценки: 4 years]

Критерии участия

Критерии включения

• Age 19 years or older
• History of ischemic stroke (cerebral infarction, transient ischemic attack, or retinal arterial ischemic event)
• Patients who meet the laboratory diagnostic criteria for antiphospholipid syndrome (APS)
• Patients or guardians who agree to the study protocol and sign with informed consent

Критерии исключения

• Patients with high-risk antiphospholipid antibody profile (triple positivity; persistent high-titers exceeding 80 U/mL of anti-cardiolipin or anti-β2 glycoprotein I antibodies)
• Systemic lupus erythematous
• Patients unable to discontinue previously taken anticoagulants or antiplatelet agents (e.g., atrial fibrillation, valvular heart disease, or a history of percutaneous coronary intervention)
• Women who are pregnant, breastfeeding, or intending to become pregnant during the study period
• Deemed unsuitable for participation in the study for more than four years, as per the investigators' discretion

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

Простое слепое

Основная цель

Профилактика

Центры проведения

South Korea · 32 центра

• Hallym University Sacred Heart Hospital — Anyang
• Busan Paik Hospital — Busan
• Pusan National University Hospital — Busan
• Chungbuk National University Hospital — Cheongju-si
• Hallym University Chuncheon Sacred Heart Hospital — Chuncheon
• Kangwon National University Hospital — Chuncheon
• Keimyung University Dongsan Medical Center — Daegu
• Yeungnam University Medical Center — Daegu
• … и ещё 24 центра

Публикации

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• Bertero MT, Bazzan M, Carignola R, Montaruli B, Silvestro E, Sciascia S, Vaccarino A, Baldovino S, Roccatello D; Antiphospholipid Piedmont Consortium. Antiphospholipid syndrome in northwest Italy (APS Piedmont Cohort): demographic features, risk factors, clinical and laboratory profile. Lupus. 2012 Jun;21(7):806-9. doi: 10.1177/0961203312446974. PMID 22635240
• Yang W, Kang MK, Ha SY, Kang DW, Bae J, Lee EJ, Jeong HY, Kim JM, Jung KH, Lee SH. Current status and role of antiphospholipid antibody testing in cryptogenic stroke. Eur J Neurol. 2022 Mar;29(3):753-760. doi: 10.1111/ene.15191. Epub 2021 Dec 3. PMID 34800314
• Cohen H, Cuadrado MJ, Erkan D, Duarte-Garcia A, Isenberg DA, Knight JS, Ortel TL, Rahman A, Salmon JE, Tektonidou MG, Williams DJ, Willis R, Woller SC, Andrade D. 16th International Congress on Antiphospholipid Antibodies Task Force Report on Antiphospholipid Syndrome Treatment Trends. Lupus. 2020 Oct;29(12):1571-1593. doi: 10.1177/0961203320950461. PMID 33100166
• Tektonidou MG, Andreoli L, Limper M, Amoura Z, Cervera R, Costedoat-Chalumeau N, Cuadrado MJ, Dorner T, Ferrer-Oliveras R, Hambly K, Khamashta MA, King J, Marchiori F, Meroni PL, Mosca M, Pengo V, Raio L, Ruiz-Irastorza G, Shoenfeld Y, Stojanovich L, Svenungsson E, Wahl D, Tincani A, Ward MM. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis. 2019 Oct;7 PMID 31092409
• Keeling D, Mackie I, Moore GW, Greer IA, Greaves M; British Committee for Standards in Haematology. Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol. 2012 Apr;157(1):47-58. doi: 10.1111/j.1365-2141.2012.09037.x. Epub 2012 Feb 8. No abstract available. PMID 22313321
• Rosove MH, Brewer PM. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med. 1992 Aug 15;117(4):303-8. doi: 10.7326/0003-4819-117-4-303. PMID 1637025
• Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GR. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med. 1995 Apr 13;332(15):993-7. doi: 10.1056/NEJM199504133321504. PMID 7885428

Идентификаторы

NCT: NCT05995600 · H-2304-096-1425

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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