xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05995600</url>
    </required_header>
    <id_info>
      <org_study_id>H-2304-096-1425</org_study_id>
      <nct_id>NCT05995600</nct_id>
    </id_info>
    <brief_title>Comparison of Clopidogrel-based Antiplatelet Therapy Versus Warfarin as Secondary Prevention Strategy for AntiPhospholipid Syndrome-related STROKE</brief_title>
    <acronym>APS-STROKE</acronym>
    <official_title>Comparison of Clopidogrel-based Antiplatelet Therapy Versus Warfarin as Secondary Prevention Strategy for AntiPhospholipid Syndrome-related STROKE (APS-STROKE)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Seoul National University Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Samjin Pharmaceutical Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Seoul National University Hospital</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Antiphospholipid syndrome (APS) has a close association with ischemic stroke; however, the&#xD;
        optimal treatment strategy for APS-related stroke has yet to be established. The clinical&#xD;
        guidelines suggest using warfarin for APS-related stroke, but these suggestions are largely&#xD;
        based on retrospective studies from the 1990s and expert opinion, rather than high-quality&#xD;
        clinical trials. Moreover, the evidence on the role of antiplatelet drugs other than aspirin&#xD;
        (e.g., clopidogrel) in APS-related stroke is particularly limited. Considering the relatively&#xD;
        young age of patients with APS and the high clinical burden of using warfarin, it is&#xD;
        necessary to verify whether warfarin is essential. Thus, the investigators aim to compare&#xD;
        clopidogrel-based antiplatelet therapy and warfarin as a secondary preventive medication for&#xD;
        patients with APS-related stroke. APS-STROKE is an exploratory, multicenter, prospective,&#xD;
        randomized, open, blinded-endpoint clinical trial. Adult patients with definite APS who have&#xD;
        a history of ischemic stroke will be included. Patients with high-risk APS (triple positivity&#xD;
        or persistently high titers of anti-cardiolipin or anti-β2-glycoprotein I antibodies),&#xD;
        systemic lupus erythematous, or indications for continued antiplatelet or anticoagulant&#xD;
        therapy will be excluded. Eligible patients will be 1:1 randomized to receive&#xD;
        clopidogrel-based antiplatelet therapy or warfarin. Patients assigned to the&#xD;
        clopidogrel-based antiplatelet therapy group will be permitted to use additional antiplatelet&#xD;
        drugs other than clopidogrel at the investigator's discretion. The primary outcome is a&#xD;
        composite of any death, major adverse cardiovascular events, systemic thromboembolic events,&#xD;
        and major bleeding during a follow-up period of at least 2 years. This study would provide&#xD;
        valuable information for determining the optimal secondary prevention strategy for&#xD;
        APS-related stroke.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">May 2028</completion_date>
    <primary_completion_date type="Anticipated">February 2027</primary_completion_date>
    <phase>Phase 4</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Prevention</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
      <masking_description>Prospective, Randomized, Open-label, Blinded Endpoint (PROBE) trial</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Composite endpoint</measure>
      <time_frame>2 years</time_frame>
      <description>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.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>MACE</measure>
      <time_frame>2 years</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ischemic stroke</measure>
      <time_frame>2 years</time_frame>
      <description>Ischemic stroke or transient ischemic attack</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Any bleeding</measure>
      <time_frame>2 years</time_frame>
      <description>Major or minor bleeding according to definitions from BARC</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Major bleeding</measure>
      <time_frame>2 years</time_frame>
      <description>BARC bleeding type 3 or 5</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intracranial bleeding</measure>
      <time_frame>2 years</time_frame>
      <description>Intracranial bleeding that is objectively confirmed by brain imaging</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinically relevant non-major bleeding</measure>
      <time_frame>2 years</time_frame>
      <description>Any bleeding that does not fit the criteria for major bleeding but does meet at least one of the following criteria:&#xD;
  requiring nonsurgical, medical intervention by a healthcare professional&#xD;
  leading to hospitalization or increased level of care&#xD;
  prompting evaluation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Any death</measure>
      <time_frame>2 years</time_frame>
      <description>Death from any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Thrombosis-related death</measure>
      <time_frame>2 years</time_frame>
      <description>Death from arterial, venous, or capillary thrombotic events</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">400</enrollment>
    <condition>Antiphospholipid Syndrome</condition>
    <condition>Ischemic Stroke</condition>
    <condition>Transient Ischemic Attack</condition>
    <condition>Cerebrovascular Disease</condition>
    <condition>Cardiovascular Diseases</condition>
    <condition>Major Bleed</condition>
    <arm_group>
      <arm_group_label>Clopidogrel-based antiplatelet therapy group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Clopidogrel 75 mg daily&#xD;
  Patients assigned to this group will be permitted to use additional antiplatelet drugs other than clopidogrel at the investigator's discretion.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Warfarin group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Warfarin (target prothrombin time-international normalized ratio 2.0-3.0)</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Antiplatelet Drug</intervention_name>
      <description>Clopidogrel ± other antiplatelet drug</description>
      <arm_group_label>Clopidogrel-based antiplatelet therapy group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Warfarin</intervention_name>
      <description>Warfarin (target prothrombin time-international normalized ratio 2.0-3.0)</description>
      <arm_group_label>Warfarin group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age 19 years or older&#xD;
  &#xD;
            -  History of ischemic stroke (cerebral infarction, transient ischemic attack, or retinal&#xD;
               arterial ischemic event)&#xD;
  &#xD;
            -  Patients who meet the laboratory diagnostic criteria for antiphospholipid syndrome&#xD;
               (APS)&#xD;
  &#xD;
            -  Patients or guardians who agree to the study protocol and sign with informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients with high-risk antiphospholipid antibody profile (triple positivity;&#xD;
               persistent high-titers exceeding 80 U/mL of anti-cardiolipin or anti-β2 glycoprotein I&#xD;
               antibodies)&#xD;
  &#xD;
            -  Systemic lupus erythematous&#xD;
  &#xD;
            -  Patients unable to discontinue previously taken anticoagulants or antiplatelet agents&#xD;
               (e.g., atrial fibrillation, valvular heart disease, or a history of percutaneous&#xD;
               coronary intervention)&#xD;
  &#xD;
            -  Women who are pregnant, breastfeeding, or intending to become pregnant during the&#xD;
               study period&#xD;
  &#xD;
            -  Deemed unsuitable for participation in the study for more than two years, as per the&#xD;
               investigators' discretion&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>19 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Seung-Hoon Lee, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Seoul National University Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Wookjin Yang, MD</last_name>
      <phone>+82-2-2072-2114</phone>
      <email>ywj_2002@naver.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Seung-Hoon Lee, MD, PhD</last_name>
      <phone>+82-2-2072-1014</phone>
      <email>sb0516@snu.ac.kr</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Hallym University Sacred Heart Hospital</name>
        <address>
          <city>Anyang</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Busan Paik Hospital</name>
        <address>
          <city>Busan</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Pusan National University Hospital</name>
        <address>
          <city>Busan</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Chungbuk National University Hospital</name>
        <address>
          <city>Cheongju-si</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Hallym University Chuncheon Sacred Heart Hospital</name>
        <address>
          <city>Chuncheon</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Kangwon National University Hospital</name>
        <address>
          <city>Chuncheon</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Keimyung University Dongsan Medical Center</name>
        <address>
          <city>Daegu</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Yeungnam University Medical Center</name>
        <address>
          <city>Daegu</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Chungnam National University Hospital</name>
        <address>
          <city>Daejeon</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Myongji Hospital</name>
        <address>
          <city>Goyang</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>National Health Insurance Service Ilsan Hospital</name>
        <address>
          <city>Goyang</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Hanyang University Guri Hospital</name>
        <address>
          <city>Guri-si</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Chonnam National University Hospital</name>
        <address>
          <city>Gwangju</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Chosun University Hospital</name>
        <address>
          <city>Gwangju</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Chung-Ang University Gwangmyeong Hospital</name>
        <address>
          <city>Gwangmyeong</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Gachon University Gil Medical Center</name>
        <address>
          <city>Incheon</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Inha University Hospital</name>
        <address>
          <city>Incheon</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Jeju National University Hospital</name>
        <address>
          <city>Jeju</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Jeonbuk National University Hospital</name>
        <address>
          <city>Jeonju</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Chungnam National University Sejong Hospital</name>
        <address>
          <city>Sejong</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Seoul National University Bundang Hospital</name>
        <address>
          <city>Seongnam</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Asan Medical Center</name>
        <address>
          <city>Seoul</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Chung-Ang University Hospital</name>
        <address>
          <city>Seoul</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Ewha Woman University Seoul Hospital</name>
        <address>
          <city>Seoul</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Ewha Womans University Mokdong Hospital</name>
        <address>
          <city>Seoul</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Hallym University Kangdong Sacred Heart Hospital</name>
        <address>
          <city>Seoul</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Hanyang University Seoul Hospital</name>
        <address>
          <city>Seoul</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Konkuk University Medical Center</name>
        <address>
          <city>Seoul</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Korea University Anam Hospital</name>
        <address>
          <city>Seoul</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Kyung Hee University Medical Center</name>
        <address>
          <city>Seoul</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Seoul Metropolitan Government-Seoul National University Boramae Medical Center</name>
        <address>
          <city>Seoul</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Seoul National University Hospital</name>
        <address>
          <city>Seoul</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Severance Hospital</name>
        <address>
          <city>Seoul</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Uijeongbu Eulji Medical Center</name>
        <address>
          <city>Uijeongbu</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Yongin Severance Hospital</name>
        <address>
          <city>Yongin</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Korea, Republic of</country>
    </location_countries>
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    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>19934177</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>31873844</PMID>
    </reference>
    <reference>
      <citation>Ordi-Ros J, Saez-Comet L, Perez-Conesa M, Vidal X, Riera-Mestre A, Castro-Salomo A, Cuquet-Pedragosa J, Ortiz-Santamaria V, Mauri-Plana M, Sole C, Cortes-Hernandez J. Rivaroxaban Versus Vitamin K Antagonist in Antiphospholipid Syndrome: A Randomized Noninferiority Trial. Ann Intern Med. 2019 Nov 19;171(10):685-694. doi: 10.7326/M19-0291. Epub 2019 Oct 15.</citation>
      <PMID>31610549</PMID>
    </reference>
    <reference>
      <citation>Woller SC, Stevens SM, Kaplan D, Wang TF, Branch DW, Groat D, Wilson EL, Armbruster B, Aston VT, Lloyd JF, Rondina MT, Elliott CG. Apixaban compared with warfarin to prevent thrombosis in thrombotic antiphospholipid syndrome: a randomized trial. Blood Adv. 2022 Mar 22;6(6):1661-1670. doi: 10.1182/bloodadvances.2021005808.</citation>
      <PMID>34662890</PMID>
    </reference>
    <reference>
      <citation>Yang W, Kang DW, Kim JM, Jung KH, Lee SH. Neuroimaging features of antiphospholipid antibody-related stroke compared with atrial fibrillation-related stroke. Sci Rep. 2022 Jul 8;12(1):11686. doi: 10.1038/s41598-022-16019-3.</citation>
      <PMID>35804027</PMID>
    </reference>
    <reference>
      <citation>Kaatz S, Ahmad D, Spyropoulos AC, Schulman S; Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost. 2015 Nov;13(11):2119-26. doi: 10.1111/jth.13140. No abstract available.</citation>
      <PMID>26764429</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 9, 2023</study_first_submitted>
    <study_first_submitted_qc>August 9, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 15, 2023</last_update_submitted>
    <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Seoul National University Hospital</investigator_affiliation>
      <investigator_full_name>Seung-Hoon Lee</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>Antiphospholipid syndrome</keyword>
    <keyword>Ischemic stroke</keyword>
    <keyword>Secondary prevention</keyword>
    <keyword>Thrombosis</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Stroke</mesh_term>
      <mesh_term>Ischemic Stroke</mesh_term>
      <mesh_term>Ischemic Attack, Transient</mesh_term>
      <mesh_term>Cerebrovascular Disorders</mesh_term>
      <mesh_term>Cardiovascular Diseases</mesh_term>
      <mesh_term>Antiphospholipid Syndrome</mesh_term>
      <mesh_term>Syndrome</mesh_term>
      <mesh_term>Ischemia</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Warfarin</mesh_term>
      <mesh_term>Platelet Aggregation Inhibitors</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05995600
  org study id: H-2304-096-1425
  nct id: NCT05995600
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  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.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Prevention
  masking: Single (Outcomes Assessor)
  masking description: Prospective, Randomized, Open-label, Blinded Endpoint (PROBE) trial
  measure: Composite endpoint
  time frame: 2 years
  description: 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.
  measure: MACE
  time frame: 2 years
  description: 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.
  measure: Ischemic stroke
  time frame: 2 years
  description: Ischemic stroke or transient ischemic attack
  measure: Any bleeding
  time frame: 2 years
  description: Major or minor bleeding according to definitions from BARC
  measure: Major bleeding
  time frame: 2 years
  description: BARC bleeding type 3 or 5
  measure: Intracranial bleeding
  time frame: 2 years
  description: Intracranial bleeding that is objectively confirmed by brain imaging
  measure: Clinically relevant non-major bleeding
  time frame: 2 years
  description: 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.
  measure: Any death
  time frame: 2 years
  description: Death from any cause
  measure: Thrombosis-related death
  time frame: 2 years
  description: Death from arterial, venous, or capillary thrombotic events
  arm group label: Clopidogrel-based antiplatelet therapy group
  arm group type: Experimental
  description: 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.
  arm group label: Warfarin group
  arm group type: Active Comparator
  description: Warfarin (target prothrombin time-international normalized ratio 2.0-3.0)
  intervention type: Drug
  intervention name: Antiplatelet Drug
  description: Clopidogrel ± other antiplatelet drug
  arm group label: Clopidogrel-based antiplatelet therapy group
  intervention type: Drug
  intervention name: Warfarin
  description: Warfarin (target prothrombin time-international normalized ratio 2.0-3.0)
  arm group label: Warfarin group
  criteria: 
  gender: All
  minimum age: 19 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Seung-Hoon Lee, MD, PhD
  role: Principal Investigator
  affiliation: Seoul National University Hospital
  last name: Wookjin Yang, MD
  phone: +82-2-2072-2114
  email: ywj_2002@naver.com
  last name: Seung-Hoon Lee, MD, PhD
  phone: +82-2-2072-1014
  email: sb0516@snu.ac.kr
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  country: Korea, Republic of
  citation: 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.
  PMID: 16420554
  citation: 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.
  PMID: 22635240
  citation: 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.
  PMID: 34800314
  citation: 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.
  PMID: 33100166
  citation: 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.
  PMID: 31092409
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  PMID: 22313321
  citation: 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.
  PMID: 1637025
  citation: 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.
  PMID: 7885428
  citation: 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.
  PMID: 9382667
  citation: 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. Erratum In: Stroke. 2021 Jul;52(7):e483-e484.
  PMID: 34024117
  citation: 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.
  PMID: 23803136
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  PMID: 29766750
  citation: 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.
  PMID: 30002145
  citation: 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.
  PMID: 19934177
  citation: 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.
  PMID: 31873844
  citation: Ordi-Ros J, Saez-Comet L, Perez-Conesa M, Vidal X, Riera-Mestre A, Castro-Salomo A, Cuquet-Pedragosa J, Ortiz-Santamaria V, Mauri-Plana M, Sole C, Cortes-Hernandez J. Rivaroxaban Versus Vitamin K Antagonist in Antiphospholipid Syndrome: A Randomized Noninferiority Trial. Ann Intern Med. 2019 Nov 19;171(10):685-694. doi: 10.7326/M19-0291. Epub 2019 Oct 15.
  PMID: 31610549
  citation: Woller SC, Stevens SM, Kaplan D, Wang TF, Branch DW, Groat D, Wilson EL, Armbruster B, Aston VT, Lloyd JF, Rondina MT, Elliott CG. Apixaban compared with warfarin to prevent thrombosis in thrombotic antiphospholipid syndrome: a randomized trial. Blood Adv. 2022 Mar 22;6(6):1661-1670. doi: 10.1182/bloodadvances.2021005808.
  PMID: 34662890
  citation: Yang W, Kang DW, Kim JM, Jung KH, Lee SH. Neuroimaging features of antiphospholipid antibody-related stroke compared with atrial fibrillation-related stroke. Sci Rep. 2022 Jul 8;12(1):11686. doi: 10.1038/s41598-022-16019-3.
  PMID: 35804027
  citation: Kaatz S, Ahmad D, Spyropoulos AC, Schulman S; Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost. 2015 Nov;13(11):2119-26. doi: 10.1111/jth.13140. No abstract available.
  PMID: 26764429
  responsible party type: Principal Investigator
  investigator affiliation: Seoul National University Hospital
  investigator full name: Seung-Hoon Lee
  investigator title: Professor
  mesh term: Stroke
  mesh term: Ischemic Stroke
  mesh term: Ischemic Attack, Transient
  mesh term: Cerebrovascular Disorders
  mesh term: Cardiovascular Diseases
  mesh term: Antiphospholipid Syndrome
  mesh term: Syndrome
  mesh term: Ischemia
  mesh term: Warfarin
  mesh term: Platelet Aggregation Inhibitors
  sharing ipd: No