Comparison of Clopidogrel-based Antiplatelet Therapy Versus Warfarin As Secondary Prevention Strategy for AntiPhospholipid Syndrome-related STROKE
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Antiplatelet Drug, Warfarin.
- Who it may be relevant to
- Registry conditions: Antiphospholipid Syndrome, Ischemic Stroke, Transient Ischemic Attack, Cerebrovascular Disease. Basic parameters: from 19 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- South Korea
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Comparison of Clopidogrel-based Antiplatelet Therapy Versus Warfarin As Secondary Prevention Strategy for AntiPhospholipid Syndrome-related STROKE (APS-STROKE)
Overview
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.
Interventions
- Drug Antiplatelet Drug
Clopidogrel ± other antiplatelet drug - Drug Warfarin
Warfarin (target prothrombin time-international normalized ratio 2.0-3.0)
Primary outcome measures
- Composite endpoint [Time frame: 4 years]
Secondary outcome measures (8)
- MACE [Time frame: 4 years]
- Ischemic stroke [Time frame: 4 years]
- Any bleeding [Time frame: 4 years]
- Major bleeding [Time frame: 4 years]
- Intracranial bleeding [Time frame: 4 years]
- Clinically relevant non-major bleeding [Time frame: 4 years]
- Any death [Time frame: 4 years]
- Thrombosis-related death [Time frame: 4 years]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Single blind
- Primary purpose
- Prevention
Study locations
South Korea · 32 centers
- 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
- … and 24 more centers
Publications
- Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295-306. doi: 10.1111/j.1538-7836.2006.01753.x. PMID 16420554
- 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
Identifiers
NCT: NCT05995600 · H-2304-096-1425