AzTrials
AzTrials

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.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

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
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
Are there results?
Not yet: the study is under way

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

Other trials in South Korea

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.

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 groups in NCT05995600
Study groupRoleWhat they receive
Clopidogrel-based antiplatelet therapy groupExperimentalClopidogrel 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 groupActive comparatorWarfarin (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.

  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.

    Measured: 4 years

Secondary outcomes (8)

  1. 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

  2. Ischemic stroke

    Ischemic stroke or transient ischemic attack

    Measured: 4 years

  3. Any bleeding

    Major or minor bleeding according to definitions from BARC

    Measured: 4 years

  4. Major bleeding

    BARC bleeding type 3 or 5

    Measured: 4 years

  5. Intracranial bleeding

    Intracranial bleeding that is objectively confirmed by brain imaging

    Measured: 4 years

  6. 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:

    1. requiring nonsurgical, medical intervention by a healthcare professional
    2. leading to hospitalization or increased level of care
    3. prompting evaluation.

    Measured: 4 years

  7. Any death

    Death from any cause

    Measured: 4 years

  8. 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.

  1. First posted16 Aug 2023
  2. Study start20 Feb 2024
  3. Primary completionJun 2029 (estimated)
  4. Study completionJun 2029 (estimated)

Resources

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)
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 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.

    PubMed 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.

    PubMed 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.

    PubMed 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;78(10):1296-1304. doi: 10.1136/annrheumdis-2019-215213. Epub 2019 May 15.

    PubMed 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.

    PubMed 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.

    PubMed 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.

    PubMed 7885428

  • Krnic-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 9382667

  • Kleindorfer 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 34024117

  • Wang 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 23803136

  • Johnston 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 29766750

  • Pengo 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 30002145

  • Erkan 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 19934177

  • Udry 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

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 11 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite endpoint (time frame: 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05995600, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in