Antiphospholipid SyndromePhase 4APS-STROKENCT05995600
Comparison of Clopidogrel-based Antiplatelet Therapy Versus Warfarin as Secondary Prevention Strategy for AntiPhospholipid Syndrome-related STROKE
A Phase 4 study testing Antiplatelet Drug and Warfarin in people with Antiphospholipid Syndrome and Ischemic Stroke, run by Seoul National University Hospital at 32 sites in South Korea.
Trial 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… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Antiphospholipid Syndrome, Ischemic Stroke, Transient Ischemic Attack
- What is being tested?
- Antiplatelet Drug and Warfarin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 32 sitesSouth Korea
- Study dates
- 20 Feb 2024to Jun 2029
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
32 sites in 1 country.
32 sites in 1 country
South Korea32 sites
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
Chungnam National University Hospital
Daejeon
Hanyang University Guri Hospital
Guri-si
Chonnam National University Hospital
Gwangju
Chosun University Hospital
Gwangju
Gachon University Gil Medical Center
Incheon
Inha University Hospital
Incheon
Jeju National University Hospital
Jeju City
Jeonbuk National University Hospital
Jeonju
Chungnam National University Sejong Hospital
Sejong
Seoul National University Bundang Hospital
Seongnam
Asan Medical Center
Seoul
Chung-Ang University Hospital
Seoul
Ewha Woman University Seoul Hospital
Seoul
Ewha Womans University Mokdong Hospital
Seoul
Hallym University Kangdong Sacred Heart Hospital
Seoul
Hanyang University Seoul Hospital
Seoul
Konkuk University Medical Center
Seoul
Korea University Anam Hospital
Seoul
Kyung Hee University Medical Center
Seoul
Seoul Metropolitan Government-Seoul National University Boramae Medical Center
Seoul
Seoul National University Hospital
Seoul
Severance Hospital
Seoul
Uijeongbu Eulji Medical Center
Uijeongbu-si
Yongin Severance Hospital
Yŏngin
About this study
Official title: Comparison of Clopidogrel-based Antiplatelet Therapy Versus Warfarin as Secondary Prevention Strategy for AntiPhospholipid Syndrome-related STROKE (APS-STROKE)
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
- Being tested
- Antiplatelet Drug, Warfarin
- Keywords
- Antiphospholipid syndrome, Ischemic stroke, Secondary prevention, Thrombosis
- Medical subject headings
- Antiphospholipid Syndrome, Ischemic Stroke, Ischemic Attack, Transient, Cerebrovascular Disorders, Cardiovascular Diseases, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antiplatelet DrugDrug
Clopidogrel ± other antiplatelet drug
WarfarinDrug
Warfarin (target prothrombin time-international normalized ratio 2.0-3.0)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Antiplatelet Drug |
| Warfarin group | Active comparator | Warfarin (target prothrombin time-international normalized ratio 2.0-3.0) Receives: Drug: Warfarin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 years
Secondary outcomes (8)
MACE
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.
Measured: 4 years
Ischemic stroke
Ischemic stroke or transient ischemic attack
Measured: 4 years
Any bleeding
Major or minor bleeding according to definitions from BARC
Measured: 4 years
Major bleeding
BARC bleeding type 3 or 5
Measured: 4 years
Intracranial bleeding
Intracranial bleeding that is objectively confirmed by brain imaging
Measured: 4 years
Clinically relevant non-major bleeding
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.
Measured: 4 years
Any death
Death from any cause
Measured: 4 years
Thrombosis-related death
Death from arterial, venous, or capillary thrombotic events
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2023
- Study start20 Feb 2024
- Primary completionJun 2029 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Antiphospholipid SyndromeStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Samjin Pharmaceutical Co., Ltd.
- Responsible party
- Principal investigator, Seung-Hoon Lee, Seoul National University Hospital
- Investigators
- Seung-Hoon Lee, MD, PhD, Principal investigator, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05995600
- Sponsor's protocol ID
- H-2304-096-1425
- Acronym
- APS-STROKE
- Status last verified
- Sep 2026
- First submitted
- 9 Aug 2023
- Last updated
- 11 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 16420554Bertero 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.
PubMed 22635240Yang 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.
PubMed 34800314Cohen 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.
PubMed 33100166Tektonidou 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;78(10):1296-1304. doi: 10.1136/annrheumdis-2019-215213. Epub 2019 May 15.
PubMed 31092409Keeling 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.
PubMed 22313321Rosove 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.
PubMed 1637025Khamashta 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.
PubMed 7885428Krnic-Barrie S, O'Connor CR, Looney SW, Pierangeli SS, Harris EN. A retrospective review of 61 patients with antiphospholipid syndrome. Analysis of factors influencing recurrent thrombosis. Arch Intern Med. 1997 Oct 13;157(18):2101-8.
PubMed 9382667Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, Kamel H, Kernan WN, Kittner SJ, Leira EC, Lennon O, Meschia JF, Nguyen TN, Pollak PM, Santangeli P, Sharrief AZ, Smith SC Jr, Turan TN, Williams LS. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2021 Jul;52(7):e364-e467. doi: 10.1161/STR.0000000000000375. Epub 2021 May 24. No abstract available.
PubMed 34024117Wang Y, Wang Y, Zhao X, Liu L, Wang D, Wang C, Wang C, Li H, Meng X, Cui L, Jia J, Dong Q, Xu A, Zeng J, Li Y, Wang Z, Xia H, Johnston SC; CHANCE Investigators. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013 Jul 4;369(1):11-9. doi: 10.1056/NEJMoa1215340. Epub 2013 Jun 26.
PubMed 23803136Johnston SC, Easton JD, Farrant M, Barsan W, Conwit RA, Elm JJ, Kim AS, Lindblad AS, Palesch YY; Clinical Research Collaboration, Neurological Emergencies Treatment Trials Network, and the POINT Investigators. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N Engl J Med. 2018 Jul 19;379(3):215-225. doi: 10.1056/NEJMoa1800410. Epub 2018 May 16.
PubMed 29766750Pengo V, Denas G, Zoppellaro G, Jose SP, Hoxha A, Ruffatti A, Andreoli L, Tincani A, Cenci C, Prisco D, Fierro T, Gresele P, Cafolla A, De Micheli V, Ghirarduzzi A, Tosetto A, Falanga A, Martinelli I, Testa S, Barcellona D, Gerosa M, Banzato A. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. 2018 Sep 27;132(13):1365-1371. doi: 10.1182/blood-2018-04-848333. Epub 2018 Jul 12.
PubMed 30002145Erkan D, Barbhaiya M, George D, Sammaritano L, Lockshin M. Moderate versus high-titer persistently anticardiolipin antibody positive patients: are they clinically different and does high-titer anti-beta 2-glycoprotein-I antibody positivity offer additional predictive information? Lupus. 2010 Apr;19(5):613-9. doi: 10.1177/0961203309355300. Epub 2009 Nov 24.
PubMed 19934177Udry S, Latino JO, Belizna C, Peres Wingeyer S, Fernandez Romero DS, de Larranaga G. A high-risk laboratory profile of antiphospholipid antibodies and thrombosis is associated with a large number of extra-criteria manifestations in obstetric antiphospholipid syndrome. Immunol Res. 2019 Dec;67(6):478-485. doi: 10.1007/s12026-019-09110-x.
PubMed 31873844