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

NCT05995600 | Recruiting Phase 4 DMC

• 1 other identifier: H-2304-096-1425
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 32

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.

Conditions

Antiphospholipid Syndrome; Ischemic Stroke; Transient Ischemic Attack; Cerebrovascular Disease; Cardiovascular Diseases; Major Bleed

Keywords

Antiphospholipid syndrome; Ischemic stroke; Secondary prevention; Thrombosis

Outcome Measures

Primary Outcomes (1)

• Composite endpoint

  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.

  4 years

Secondary Outcomes (8)

• MACE

  4 years

• Ischemic stroke

  4 years

• Any bleeding

  4 years

• Major bleeding

  4 years

• Intracranial bleeding

  4 years

Study Arms (2)

Clopidogrel-based antiplatelet therapy group

EXPERIMENTAL

Clopidogrel 75 mg daily Patients assigned to this group will be permitted to use additional antiplatelet drugs other than clopidogrel at the investigator's discretion.

Drug: Antiplatelet Drug

Warfarin group

ACTIVE COMPARATOR

Warfarin (target prothrombin time-international normalized ratio 2.0-3.0)

Drug: Warfarin

Interventions

Antiplatelet Drug DRUG

Clopidogrel ± other antiplatelet drug

Clopidogrel-based antiplatelet therapy group

Warfarin DRUG

Warfarin (target prothrombin time-international normalized ratio 2.0-3.0)

Warfarin group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Samjin Pharmaceutical Co., Ltd.: collaborator

Study Sites (32)

Hallym University Sacred Heart Hospital

Anyang, South Korea

RECRUITING

Busan Paik Hospital

Busan, South Korea

RECRUITING

Pusan National University Hospital

Busan, South Korea

RECRUITING

Chungbuk National University Hospital

Cheongju-si, South Korea

RECRUITING

Hallym University Chuncheon Sacred Heart Hospital

Chuncheon, South Korea

RECRUITING

Kangwon National University Hospital

Chuncheon, South Korea

RECRUITING

Keimyung University Dongsan Medical Center

Daegu, South Korea

RECRUITING

Yeungnam University Medical Center

Daegu, South Korea

RECRUITING

Chungnam National University Hospital

Daejeon, South Korea

RECRUITING

Hanyang University Guri Hospital

Guri-si, South Korea

RECRUITING

Chonnam National University Hospital

Gwangju, South Korea

RECRUITING

Chosun University Hospital

Gwangju, South Korea

RECRUITING

Gachon University Gil Medical Center

Incheon, South Korea

RECRUITING

Inha University Hospital

Incheon, South Korea

RECRUITING

Jeju National University Hospital

Jeju City, South Korea

RECRUITING

Jeonbuk National University Hospital

Jeonju, South Korea

RECRUITING

Chungnam National University Sejong Hospital

Sejong, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam, South Korea

RECRUITING

Asan Medical Center

Seoul, South Korea

RECRUITING

Chung-Ang University Hospital

Seoul, South Korea

RECRUITING

Ewha Woman University Seoul Hospital

Seoul, South Korea

RECRUITING

Ewha Womans University Mokdong Hospital

Seoul, South Korea

RECRUITING

Hallym University Kangdong Sacred Heart Hospital

Seoul, South Korea

RECRUITING

Hanyang University Seoul Hospital

Seoul, South Korea

RECRUITING

Konkuk University Medical Center

Seoul, South Korea

RECRUITING

Korea University Anam Hospital

Seoul, South Korea

RECRUITING

Kyung Hee University Medical Center

Seoul, South Korea

RECRUITING

Seoul Metropolitan Government-Seoul National University Boramae Medical Center

Seoul, South Korea

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

Severance Hospital

Seoul, South Korea

RECRUITING

Uijeongbu Eulji Medical Center

Uijeongbu-si, South Korea

RECRUITING

Yongin Severance Hospital

Yŏngin, South Korea

RECRUITING

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MeSH Terms

Conditions

Antiphospholipid Syndrome; Ischemic Stroke; Ischemic Attack, Transient; Cerebrovascular Disorders; Cardiovascular Diseases; Thrombosis

Interventions

Platelet Aggregation Inhibitors; Warfarin

Condition Hierarchy (Ancestors)

Autoimmune Diseases; Immune System Diseases; Stroke; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Brain Ischemia; Embolism and Thrombosis

Intervention Hierarchy (Ancestors)

Hematologic Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Seung-Hoon Lee, MD, PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wookjin Yang, MD, PhD

CONTACT

+82-2-2072-2114; ywj_2002@naver.com

Seung-Hoon Lee, MD, PhD

CONTACT

+82-2-2072-1014; sb0516@snu.ac.kr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Prospective, Randomized, Open-label, Blinded Endpoint (PROBE) trial
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 9, 2023
• First Posted: August 16, 2023
• Study Start: February 20, 2024
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: October 16, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (32)