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

Phase 4
Recruiting
Conditions
Antiphospholipid Syndrome
Ischemic Stroke
Transient Ischemic Attack
Cerebrovascular Disease
Cardiovascular Diseases
Major Bleed
Interventions
Drug: Antiplatelet Drug
Registration Number
NCT05995600
Lead Sponsor
Seoul National University Hospital
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
200
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Clopidogrel-based antiplatelet therapy groupAntiplatelet DrugClopidogrel 75 mg daily Patients assigned to this group will be permitted to use additional antiplatelet drugs other than clopidogrel at the investigator's discretion.
Warfarin groupWarfarinWarfarin (target prothrombin time-international normalized ratio 2.0-3.0)
Primary Outcome Measures
NameTimeMethod
Composite endpoint4 years

Composite endpoint of any death, major adverse cardiovascular events (MACEs), systemic thromboembolic events, and major bleeding. MACE includes any stroke, transient ischemic attack, and acute coronary syndrome (i.e., ST-elevation myocardial infarction, non-ST elevation myocardial infarction, and hospitalization with unstable angina) in this study. Major bleeding refers to bleeding events meeting the criteria for Bleeding Academic Research Consortium (BARC) type 3 or 5.

Secondary Outcome Measures
NameTimeMethod
Ischemic stroke4 years

Ischemic stroke or transient ischemic attack

Any bleeding4 years

Major or minor bleeding according to definitions from BARC

Major bleeding4 years

BARC bleeding type 3 or 5

Intracranial bleeding4 years

Intracranial bleeding that is objectively confirmed by brain imaging

MACE4 years

MACE includes any stroke, transient ischemic attack, and acute coronary syndrome (i.e., ST-elevation myocardial infarction, non-ST elevation myocardial infarction, and hospitalization with unstable angina) in this study.

Clinically relevant non-major bleeding4 years

Any bleeding that does not fit the criteria for major bleeding but does meet at least one of the following criteria:

1. requiring nonsurgical, medical intervention by a healthcare professional

2. leading to hospitalization or increased level of care

3. prompting evaluation.

Any death4 years

Death from any cause

Thrombosis-related death4 years

Death from arterial, venous, or capillary thrombotic events

Trial Locations

Locations (32)

Hallym University Sacred Heart Hospital

🇰🇷

Anyang, Korea, Republic of

Busan Paik Hospital

🇰🇷

Busan, Korea, Republic of

Yeungnam University Medical Center

🇰🇷

Daegu, Korea, Republic of

Hanyang University Guri Hospital

🇰🇷

Guri-si, Korea, Republic of

Jeju National University Hospital

🇰🇷

Jeju, Korea, Republic of

Kyung Hee University Medical Center

🇰🇷

Seoul, Korea, Republic of

Pusan National University Hospital

🇰🇷

Busan, Korea, Republic of

Hallym University Chuncheon Sacred Heart Hospital

🇰🇷

Chuncheon, Korea, Republic of

Keimyung University Dongsan Medical Center

🇰🇷

Daegu, Korea, Republic of

Chungnam National University Hospital

🇰🇷

Daejeon, Korea, Republic of

Chonnam National University Hospital

🇰🇷

Gwangju, Korea, Republic of

Gachon University Gil Medical Center

🇰🇷

Incheon, Korea, Republic of

Chosun University Hospital

🇰🇷

Gwangju, Korea, Republic of

Inha University Hospital

🇰🇷

Incheon, Korea, Republic of

Jeonbuk National University Hospital

🇰🇷

Jeonju, Korea, Republic of

Chung-Ang University Hospital

🇰🇷

Seoul, Korea, Republic of

Seoul National University Bundang Hospital

🇰🇷

Seongnam, Korea, Republic of

Ewha Woman University Seoul Hospital

🇰🇷

Seoul, Korea, Republic of

Konkuk University Medical Center

🇰🇷

Seoul, Korea, Republic of

Ewha Womans University Mokdong Hospital

🇰🇷

Seoul, Korea, Republic of

Hanyang University Seoul Hospital

🇰🇷

Seoul, Korea, Republic of

Korea University Anam Hospital

🇰🇷

Seoul, Korea, Republic of

Hallym University Kangdong Sacred Heart Hospital

🇰🇷

Seoul, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Seoul Metropolitan Government-Seoul National University Boramae Medical Center

🇰🇷

Seoul, Korea, Republic of

Uijeongbu Eulji Medical Center

🇰🇷

Uijeongbu, Korea, Republic of

Severance Hospital

🇰🇷

Seoul, Korea, Republic of

Yongin Severance Hospital

🇰🇷

Yongin, Korea, Republic of

Chungnam National University Sejong Hospital

🇰🇷

Sejong, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Chungbuk National University Hospital

🇰🇷

Cheongju-si, Korea, Republic of

Kangwon National University Hospital

🇰🇷

Chuncheon, Korea, Republic of

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