<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/NCT04436978</url>
  </required_header>
  <id_info>
    <org_study_id>NL81102.100.22</org_study_id>
    <secondary_id>2022-001298-30</secondary_id>
    <nct_id>NCT04436978</nct_id>
  </id_info>
  <brief_title>What is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Undergoing PCI?</brief_title>
  <acronym>WOEST-3</acronym>
  <official_title>What is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Having Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Antonius Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Daiichi Sankyo, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>St. Antonius 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The optimal antithrombotic management in patients with coronary artery disease (CAD) and&#xD;
      concomitant atrial fibrillation (AF) is unknown. AF patients are treated with oral&#xD;
      anticoagulation (OAC) to prevent ischemic stroke and systemic embolism and patients&#xD;
      undergoing percutaneous coronary intervention (PCI) are treated with dual antiplatelet&#xD;
      therapy (DAPT), i.e. aspirin plus P2Y12 inhibitor, to prevent stent thrombosis (ST) and&#xD;
      myocardial infarction (MI). Patients with AF undergoing PCI were traditionally treated with&#xD;
      triple antithrombotic therapy (TAT, i.e. OAC plus aspirin and P2Y12 inhibitor) to prevent&#xD;
      ischemic complications. However, TAT doubles or even triples the risk of major bleeding&#xD;
      complications. More recently, several clinical studies demonstrated that omitting aspirin, a&#xD;
      strategy known as dual antithrombotic therapy (DAT) is safer compared to TAT with comparable&#xD;
      efficacy.&#xD;
&#xD;
      However, pooled evidence from recent meta-analyses suggests that patients treated with DAT&#xD;
      are at increased risk of MI and ST. Insights from the AUGUSTUS trial showed that aspirin&#xD;
      added to OAC and clopidogrel for 30 days, but not thereafter, resulted in fewer severe&#xD;
      ischemic events. This finding emphasizes the relevance of early aspirin administration on&#xD;
      ischemic benefit, also reflected in the current ESC guideline. However, because we consider&#xD;
      the bleeding risk of TAT unacceptably high, we propose to use a short course of DAPT&#xD;
      (omitting OAC for 1 month). There is evidence from the BRIDGE study that a short period of&#xD;
      omitting OAC is safe in patients with AF. In this study, these patients are treated with&#xD;
      DAPT, which also prevents stroke, albeit not as effective as OAC. This temporary interruption&#xD;
      of OAC will allow aspirin treatment in the first month post-PCI where the risk of both&#xD;
      bleeding and stent thrombosis is greatest.&#xD;
&#xD;
      The WOEST 3 trial is a multicentre, open-label, randomised controlled trial investigating the&#xD;
      safety and efficacy of one month DAPT compared to guideline-directed therapy consisting of&#xD;
      OAC and P2Y12 inhibitor combined with aspirin up to 30 days. We hypothesise that the use of&#xD;
      short course DAPT is superior in bleeding and non-inferior in preventing ischemic events. The&#xD;
      primary safety endpoint is major or clinically relevant non-major bleeding as defined by the&#xD;
      ISTH at 6 weeks after PCI. The primary efficacy endpoint is a composite of all-cause death,&#xD;
      myocardial infarction, stroke, systemic embolism, or stent thrombosis at 6 weeks after PCI.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 11, 2023</start_date>
  <completion_date type="Anticipated">December 1, 2027</completion_date>
  <primary_completion_date type="Anticipated">October 1, 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>
    <intervention_model_description>The study is designed as a multicentre open label randomized controlled superiority trial with regards to safety and non-inferiority trial with regards to efficacy.&#xD;
Participating study centres will enrol patients undergoing PCI who have previously or newly diagnosed AF and indication for NOAC. As soon as possible, but within 72 hours after PCI, patients will be randomized 1:1 to either&#xD;
30 days DAPT (asprin + P2Y12 inhibitor), followed by guideline-directed therapy (edoxaban + P2Y12 inhibitor)&#xD;
Standard guideline-directed therapy (edoxaban + P2Y12 inhibitor, aspirin limited to in-hospital use or up to 30 days in selected high-risk patients)</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary safety endpoint</measure>
    <time_frame>6 weeks</time_frame>
    <description>Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Primary efficacy endpoint</measure>
    <time_frame>6 weeks</time_frame>
    <description>Composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Bleeding complications</measure>
    <time_frame>6 months</time_frame>
    <description>Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Thrombotic complications</measure>
    <time_frame>6 months</time_frame>
    <description>Composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Net clinical benefit</measure>
    <time_frame>6 weeks, 3 months, 6 months</time_frame>
    <description>Composite of major bleeding, myocardial infarction, stroke, systemic embolism all-cause death and stent thrombosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical symptom severity</measure>
    <time_frame>6 weeks, 3 months, 6 months</time_frame>
    <description>CCS grade</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause death</measure>
    <time_frame>6 weeks, 3 months, 6 months</time_frame>
    <description>All-cause death as defined by ARC-2 and SCTI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Myocardial infarction</measure>
    <time_frame>6 weeks, 3 months, 6 months</time_frame>
    <description>Myocardial infarction as defined by the 4th Universal Definition of Myocardial Infarction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stroke</measure>
    <time_frame>6 weeks, 3 months, 6 months</time_frame>
    <description>Stroke as defined by VARC-2 definitions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic embolism</measure>
    <time_frame>6 weeks, 3 months, 6 months</time_frame>
    <description>Systemic embolism according to ENTRUST-AF PCI definition</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stent thrombosis</measure>
    <time_frame>6 weeks, 3 months, 6 months</time_frame>
    <description>Stent thrombosis as defined by ARC-2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major bleeding</measure>
    <time_frame>6 weeks, 3 months, 6 months</time_frame>
    <description>Major bleeding as defined by BARC 3 or 5</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinically relevant non-major bleeding</measure>
    <time_frame>6 weeks, 3 months, 6 months</time_frame>
    <description>CRNM as defined by BARC 2</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Quality of life as assessed by the EuroQol-5D-5L questionnaire</measure>
    <time_frame>6 weeks, 3 months, 6 months</time_frame>
    <description>EuroQol-5D-5L questionnaire</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">2000</enrollment>
  <condition>Acute Coronary Syndrome</condition>
  <condition>Myocardial Infarction</condition>
  <condition>Atrial Fibrillation</condition>
  <condition>Atrial Flutter</condition>
  <condition>STEMI - ST Elevation Myocardial Infarction</condition>
  <condition>NSTEMI - Non-ST Segment Elevation MI</condition>
  <condition>Bleeding</condition>
  <condition>Stroke</condition>
  <condition>Stent Thrombosis</condition>
  <condition>Embolism</condition>
  <condition>Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>First month DAPT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>30-day DAPT (aspirin + P2Y12 inhibitor). After 30 days all patients will be treated with edoxaban and P2Y12 inhibitor.&#xD;
Selection of P2Y12 inhibitor is at the discretion of the treating physician, depending on both bleeding and ischemic risk. Dosage of aspirin and P2Y12 inhibitor is according to local guidelines.&#xD;
NOAC of choice will be edoxaban. Patients will be treated with the recommended dose of 60mg once daily or the reduced dose of 30mg once daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Guideline-directed therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard guideline-directed therapy (edoxaban + P2Y12 inhibitor, aspirin limited to in-hospital use or up to 30 days in selected high-risk patients). After 30 days all patients will be treated with edoxaban and P2Y12 inhibitor.&#xD;
Selection of P2Y12 inhibitor is at the discretion of the treating physician, depending on both bleeding and ischemic risk. Dosage of aspirin and P2Y12 inhibitor is according to local guidelines.&#xD;
NOAC of choice will be edoxaban. Patients will be treated with the recommended dose of 60mg once daily or the reduced dose of 30mg once daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>30-day DAPT</intervention_name>
    <description>DAPT (aspirin + P2Y12 inhibitor) during the first 30 days following PCI. After 30 days, all patients will be treated with edoxaban and a P2Y12 inhibitor.</description>
    <arm_group_label>First month DAPT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Guideline-directed therapy</intervention_name>
    <description>Guideline-directed therapy (edoxaban + P2Y12 inhibitor, aspirin limited to in-hospital use or up to 30 days in selected high-risk patients)</description>
    <arm_group_label>Guideline-directed therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients ≥ 18 years&#xD;
&#xD;
          2. Undergoing successful PCI (either ACS or elective PCI)&#xD;
&#xD;
          3. History of or newly diagnosed (&lt;72 hours after PCI/ACS) atrial fibrillation or flutter&#xD;
             with a long-term (≥ 1 year) indication for OAC&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Contra indication to edoxaban, aspirin or all P2Y12 inhibitors&#xD;
&#xD;
          2. Current indication for OAC besides atrial fibrillation/flutter (e.g. venous&#xD;
             thromboembolism)&#xD;
&#xD;
          3. &lt;12 months after any stroke&#xD;
&#xD;
          4. CHADSVASc score ≥7&#xD;
&#xD;
          5. Moderate to severe mitral valve stenosis (AVA ≤1.5 cm2)&#xD;
&#xD;
          6. Mechanical heart valve prosthesis&#xD;
&#xD;
          7. Intracardiac thrombus or apical aneurysm requiring OAC&#xD;
&#xD;
          8. Poor LV function (LVEF &lt;30%) with proven slow-flow&#xD;
&#xD;
          9. History of intracranial haemorrhage&#xD;
&#xD;
         10. Active bleeding on randomization&#xD;
&#xD;
         11. History of intraocular, spinal, retroperitoneal, or traumatic intra-articular&#xD;
             bleeding, unless the causative factor has been permanently resolved&#xD;
&#xD;
         12. Recent (&lt;1 month) gastrointestinal haemorrhage, unless the causative factor has been&#xD;
             permanently resolved.&#xD;
&#xD;
         13. Known coagulopathy&#xD;
&#xD;
         14. Severe anaemia requiring blood transfusion or thrombocytopenia &lt;50 × 109/L&#xD;
&#xD;
         15. BMI &gt;40 or bariatric surgery&#xD;
&#xD;
         16. Kidney failure (eGFR &lt;15)&#xD;
&#xD;
         17. Active liver disease (ALT, ASP, AP &gt;3x ULN or active hepatitis A, B or C)&#xD;
&#xD;
         18. Active malignancy excluding non-melanoma skin cancer&#xD;
&#xD;
         19. Life expectancy &lt;1 year&#xD;
&#xD;
         20. Pregnancy or breast-feeding women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jurriën M ten Berg, Prof, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Antonius Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ashley Verburg, MD</last_name>
    <phone>+31 (0)88 320 0925</phone>
    <email>as.verburg@antoniusziekenhuis.nl</email>
  </overall_contact>
  <location>
    <facility>
      <name>ASZ Aalst</name>
      <address>
        <city>Aalst</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rosseel</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>UZ Antwerpen</name>
      <address>
        <city>Antwerpen</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vandendriessche</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Imelda Ziekenhuis</name>
      <address>
        <city>Bonheiden</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dewilde</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>UZ Brussel</name>
      <address>
        <city>Brussel</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Vandeloo</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ziekenhuis Oost-Limburg</name>
      <address>
        <city>Genk</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ferdinande</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>AZ Maria Middelares Gent</name>
      <address>
        <city>Gent</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cornelis</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Jan Yperman</name>
      <address>
        <city>Ieper</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>De Keyser</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>AZ Groeninge</name>
      <address>
        <city>Kortrijk</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>van mieghem, MD PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Adriaenssens</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>AZ Delta</name>
      <address>
        <city>Roeselare</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dujardin</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Noordwest Ziekenhuisgroep</name>
      <address>
        <city>Alkmaar</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Heestermans</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Amsterdam UMC</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Simao Henriques, MD PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>OLVG</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vink</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hagaziekenhuis</name>
      <address>
        <city>Den Haag</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Schotborgh</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Treant Zorggroep</name>
      <address>
        <city>Emmen</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ruifrok</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Tergooi MC</name>
      <address>
        <city>Hilversum</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Plomp</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>St. Antonius Hospital</name>
      <address>
        <city>Nieuwegein</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jurrien ten berg, MD PhD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>September 5, 2023</last_update_submitted>
  <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>St. Antonius Hospital</investigator_affiliation>
    <investigator_full_name>Jurriën M. ten Berg, MD, PhD</investigator_full_name>
    <investigator_title>Professor dr.</investigator_title>
  </responsible_party>
  <keyword>Acute Coronary Syndrome</keyword>
  <keyword>Myocardial Infarction</keyword>
  <keyword>Atrial Fibrillation</keyword>
  <keyword>Atrial Flutter</keyword>
  <keyword>STEMI - ST Elevation Myocardial Infarction</keyword>
  <keyword>NSTEMI - Non-ST Segment Elevation MI</keyword>
  <keyword>Oral Anticoagulant</keyword>
  <keyword>NOAC - Novel Oral Anticoagulant</keyword>
  <keyword>DOAC - Direct Oral Anticoagulant</keyword>
  <keyword>DAPT - Dual Antiplatelet Therapy</keyword>
  <keyword>Antithrombotic Therapy</keyword>
  <keyword>Dual Therapy</keyword>
  <keyword>Triple Therapy</keyword>
  <keyword>Bleeding</keyword>
  <keyword>Thrombosis</keyword>
  <keyword>Stroke</keyword>
  <keyword>Stent Thrombosis</keyword>
  <keyword>Systemic Embolism</keyword>
  <keyword>Percutaneous coronary intervention</keyword>
  <keyword>Coronary artery disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Acute Coronary Syndrome</mesh_term>
    <mesh_term>Embolism</mesh_term>
    <mesh_term>ST Elevation Myocardial Infarction</mesh_term>
    <mesh_term>Atrial Flutter</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Infarction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Will individual participant data be available? Yes&#xD;
What data in particular will be shared? Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).&#xD;
What other documents will be available? Study Protocol, informed consent form, clinical study report&#xD;
When will data be available (start and end dates)? Within 1 year following article publication. End date to be determined.&#xD;
With whom? Researchers who provide a methodologically sound proposal.&#xD;
For what types of analyses? To achieve aims in the approved proposal.&#xD;
By what mechanism will data be made available? Proposals should be directed to as.verburg@antoniusziekenhuis.nl. To gain access, data requestors will need to sign a data access agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Within 1 year following article publication. End date to be determined.</ipd_time_frame>
    <ipd_access_criteria>Researchers who provide a methodologically sound proposal.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04436978
org study id: NL81102.100.22
secondary id: 2022-001298-30
nct id: NCT04436978
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The optimal antithrombotic management in patients with coronary artery disease (CAD) and
      concomitant atrial fibrillation (AF) is unknown. AF patients are treated with oral
      anticoagulation (OAC) to prevent ischemic stroke and systemic embolism and patients
      undergoing percutaneous coronary intervention (PCI) are treated with dual antiplatelet
      therapy (DAPT), i.e. aspirin plus P2Y12 inhibitor, to prevent stent thrombosis (ST) and
      myocardial infarction (MI). Patients with AF undergoing PCI were traditionally treated with
      triple antithrombotic therapy (TAT, i.e. OAC plus aspirin and P2Y12 inhibitor) to prevent
      ischemic complications. However, TAT doubles or even triples the risk of major bleeding
      complications. More recently, several clinical studies demonstrated that omitting aspirin, a
      strategy known as dual antithrombotic therapy (DAT) is safer compared to TAT with comparable
      efficacy.

      However, pooled evidence from recent meta-analyses suggests that patients treated with DAT
      are at increased risk of MI and ST. Insights from the AUGUSTUS trial showed that aspirin
      added to OAC and clopidogrel for 30 days, but not thereafter, resulted in fewer severe
      ischemic events. This finding emphasizes the relevance of early aspirin administration on
      ischemic benefit, also reflected in the current ESC guideline. However, because we consider
      the bleeding risk of TAT unacceptably high, we propose to use a short course of DAPT
      (omitting OAC for 1 month). There is evidence from the BRIDGE study that a short period of
      omitting OAC is safe in patients with AF. In this study, these patients are treated with
      DAPT, which also prevents stroke, albeit not as effective as OAC. This temporary interruption
      of OAC will allow aspirin treatment in the first month post-PCI where the risk of both
      bleeding and stent thrombosis is greatest.

      The WOEST 3 trial is a multicentre, open-label, randomised controlled trial investigating the
      safety and efficacy of one month DAPT compared to guideline-directed therapy consisting of
      OAC and P2Y12 inhibitor combined with aspirin up to 30 days. We hypothesise that the use of
      short course DAPT is superior in bleeding and non-inferior in preventing ischemic events. The
      primary safety endpoint is major or clinically relevant non-major bleeding as defined by the
      ISTH at 6 weeks after PCI. The primary efficacy endpoint is a composite of all-cause death,
      myocardial infarction, stroke, systemic embolism, or stent thrombosis at 6 weeks after PCI.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The study is designed as a multicentre open label randomized controlled superiority trial with regards to safety and non-inferiority trial with regards to efficacy.
Participating study centres will enrol patients undergoing PCI who have previously or newly diagnosed AF and indication for NOAC. As soon as possible, but within 72 hours after PCI, patients will be randomized 1:1 to either
30 days DAPT (asprin + P2Y12 inhibitor), followed by guideline-directed therapy (edoxaban + P2Y12 inhibitor)
Standard guideline-directed therapy (edoxaban + P2Y12 inhibitor, aspirin limited to in-hospital use or up to 30 days in selected high-risk patients)
primary purpose: Prevention
masking: Single (Outcomes Assessor)
measure: Primary safety endpoint
time frame: 6 weeks
description: Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis
measure: Primary efficacy endpoint
time frame: 6 weeks
description: Composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis
measure: Bleeding complications
time frame: 6 months
description: Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis
measure: Thrombotic complications
time frame: 6 months
description: Composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis
measure: Net clinical benefit
time frame: 6 weeks, 3 months, 6 months
description: Composite of major bleeding, myocardial infarction, stroke, systemic embolism all-cause death and stent thrombosis
measure: Clinical symptom severity
time frame: 6 weeks, 3 months, 6 months
description: CCS grade
measure: All-cause death
time frame: 6 weeks, 3 months, 6 months
description: All-cause death as defined by ARC-2 and SCTI
measure: Myocardial infarction
time frame: 6 weeks, 3 months, 6 months
description: Myocardial infarction as defined by the 4th Universal Definition of Myocardial Infarction
measure: Stroke
time frame: 6 weeks, 3 months, 6 months
description: Stroke as defined by VARC-2 definitions
measure: Systemic embolism
time frame: 6 weeks, 3 months, 6 months
description: Systemic embolism according to ENTRUST-AF PCI definition
measure: Stent thrombosis
time frame: 6 weeks, 3 months, 6 months
description: Stent thrombosis as defined by ARC-2
measure: Major bleeding
time frame: 6 weeks, 3 months, 6 months
description: Major bleeding as defined by BARC 3 or 5
measure: Clinically relevant non-major bleeding
time frame: 6 weeks, 3 months, 6 months
description: CRNM as defined by BARC 2
measure: Quality of life as assessed by the EuroQol-5D-5L questionnaire
time frame: 6 weeks, 3 months, 6 months
description: EuroQol-5D-5L questionnaire
arm group label: First month DAPT
arm group type: Active Comparator
description: 30-day DAPT (aspirin + P2Y12 inhibitor). After 30 days all patients will be treated with edoxaban and P2Y12 inhibitor.
Selection of P2Y12 inhibitor is at the discretion of the treating physician, depending on both bleeding and ischemic risk. Dosage of aspirin and P2Y12 inhibitor is according to local guidelines.
NOAC of choice will be edoxaban. Patients will be treated with the recommended dose of 60mg once daily or the reduced dose of 30mg once daily.
arm group label: Guideline-directed therapy
arm group type: Active Comparator
description: Standard guideline-directed therapy (edoxaban + P2Y12 inhibitor, aspirin limited to in-hospital use or up to 30 days in selected high-risk patients). After 30 days all patients will be treated with edoxaban and P2Y12 inhibitor.
Selection of P2Y12 inhibitor is at the discretion of the treating physician, depending on both bleeding and ischemic risk. Dosage of aspirin and P2Y12 inhibitor is according to local guidelines.
NOAC of choice will be edoxaban. Patients will be treated with the recommended dose of 60mg once daily or the reduced dose of 30mg once daily.
intervention type: Drug
intervention name: 30-day DAPT
description: DAPT (aspirin + P2Y12 inhibitor) during the first 30 days following PCI. After 30 days, all patients will be treated with edoxaban and a P2Y12 inhibitor.
arm group label: First month DAPT
intervention type: Drug
intervention name: Guideline-directed therapy
description: Guideline-directed therapy (edoxaban + P2Y12 inhibitor, aspirin limited to in-hospital use or up to 30 days in selected high-risk patients)
arm group label: Guideline-directed therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jurriën M ten Berg, Prof, MD
role: Principal Investigator
affiliation: St. Antonius Hospital
last name: Ashley Verburg, MD
phone: +31 (0)88 320 0925
email: as.verburg@antoniusziekenhuis.nl
facility: 
status: Recruiting
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country: Belgium
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: St. Antonius Hospital
investigator full name: Jurriën M. ten Berg, MD, PhD
investigator title: Professor dr.
mesh term: Atrial Fibrillation
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease
mesh term: Myocardial Infarction
mesh term: Thrombosis
mesh term: Acute Coronary Syndrome
mesh term: Embolism
mesh term: ST Elevation Myocardial Infarction
mesh term: Atrial Flutter
mesh term: Syndrome
mesh term: Infarction
sharing ipd: Yes
ipd description: Will individual participant data be available? Yes
What data in particular will be shared? Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
What other documents will be available? Study Protocol, informed consent form, clinical study report
When will data be available (start and end dates)? Within 1 year following article publication. End date to be determined.
With whom? Researchers who provide a methodologically sound proposal.
For what types of analyses? To achieve aims in the approved proposal.
By what mechanism will data be made available? Proposals should be directed to as.verburg@antoniusziekenhuis.nl. To gain access, data requestors will need to sign a data access agreement.
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Within 1 year following article publication. End date to be determined.
ipd access criteria: Researchers who provide a methodologically sound proposal.