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

Sponsor

Seoul National University Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05995600

Collaborator

Samjin Pharmaceutical Co., Ltd. (Industry)

400

Enrollment

Locations

Arms

Anticipated Duration (Months)

11.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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 2 years. This study would provide valuable information for determining the optimal secondary prevention strategy for APS-related stroke.

Condition or Disease	Intervention/Treatment	Phase
Antiphospholipid Syndrome Ischemic Stroke Transient Ischemic Attack Cerebrovascular Disease Cardiovascular Diseases Major Bleed	Drug: Antiplatelet Drug Drug: Warfarin	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Masking Description:

Prospective, Randomized, Open-label, Blinded Endpoint (PROBE) trial

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Feb 1, 2027

Anticipated Study Completion Date :

May 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clopidogrel-based antiplatelet therapy group 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 Clopidogrel ± other antiplatelet drug
Active Comparator: Warfarin group Warfarin (target prothrombin time-international normalized ratio 2.0-3.0)	Drug: Warfarin Warfarin (target prothrombin time-international normalized ratio 2.0-3.0)

Arm

Intervention/Treatment

Experimental: Clopidogrel-based antiplatelet therapy group

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

Clopidogrel ± other antiplatelet drug

Active Comparator: Warfarin group

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

Drug: Warfarin

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

Outcome Measures

Primary Outcome Measures

Composite endpoint [2 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

MACE [2 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.
Ischemic stroke [2 years]
Ischemic stroke or transient ischemic attack
Any bleeding [2 years]
Major or minor bleeding according to definitions from BARC
Major bleeding [2 years]
BARC bleeding type 3 or 5
Intracranial bleeding [2 years]
Intracranial bleeding that is objectively confirmed by brain imaging
Clinically relevant non-major bleeding [2 years]
Any bleeding that does not fit the criteria for major bleeding but does meet at least one of the following criteria: requiring nonsurgical, medical intervention by a healthcare professional leading to hospitalization or increased level of care prompting evaluation.
Any death [2 years]
Death from any cause
Thrombosis-related death [2 years]
Death from arterial, venous, or capillary thrombotic events

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 two years, as per the investigators' discretion

Contacts and Locations

Locations

	Site	City	Country
1	Hallym University Sacred Heart Hospital	Anyang	Korea, Republic of
2	Busan Paik Hospital	Busan	Korea, Republic of
3	Pusan National University Hospital	Busan	Korea, Republic of
4	Chungbuk National University Hospital	Cheongju-si	Korea, Republic of
5	Hallym University Chuncheon Sacred Heart Hospital	Chuncheon	Korea, Republic of
6	Kangwon National University Hospital	Chuncheon	Korea, Republic of
7	Keimyung University Dongsan Medical Center	Daegu	Korea, Republic of
8	Yeungnam University Medical Center	Daegu	Korea, Republic of
9	Chungnam National University Hospital	Daejeon	Korea, Republic of
10	Myongji Hospital	Goyang	Korea, Republic of
11	National Health Insurance Service Ilsan Hospital	Goyang	Korea, Republic of
12	Hanyang University Guri Hospital	Guri-si	Korea, Republic of
13	Chonnam National University Hospital	Gwangju	Korea, Republic of
14	Chosun University Hospital	Gwangju	Korea, Republic of
15	Chung-Ang University Gwangmyeong Hospital	Gwangmyeong	Korea, Republic of
16	Gachon University Gil Medical Center	Incheon	Korea, Republic of
17	Inha University Hospital	Incheon	Korea, Republic of
18	Jeju National University Hospital	Jeju	Korea, Republic of
19	Jeonbuk National University Hospital	Jeonju	Korea, Republic of
20	Chungnam National University Sejong Hospital	Sejong	Korea, Republic of
21	Seoul National University Bundang Hospital	Seongnam	Korea, Republic of
22	Asan Medical Center	Seoul	Korea, Republic of
23	Chung-Ang University Hospital	Seoul	Korea, Republic of
24	Ewha Woman University Seoul Hospital	Seoul	Korea, Republic of
25	Ewha Womans University Mokdong Hospital	Seoul	Korea, Republic of
26	Hallym University Kangdong Sacred Heart Hospital	Seoul	Korea, Republic of
27	Hanyang University Seoul Hospital	Seoul	Korea, Republic of
28	Konkuk University Medical Center	Seoul	Korea, Republic of
29	Korea University Anam Hospital	Seoul	Korea, Republic of
30	Kyung Hee University Medical Center	Seoul	Korea, Republic of
31	Seoul Metropolitan Government-Seoul National University Boramae Medical Center	Seoul	Korea, Republic of
32	Seoul National University Hospital	Seoul	Korea, Republic of
33	Severance Hospital	Seoul	Korea, Republic of
34	Uijeongbu Eulji Medical Center	Uijeongbu	Korea, Republic of
35	Yongin Severance Hospital	Yongin	Korea, Republic of