<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/NCT03244319</url>
  </required_header>
  <id_info>
    <org_study_id>4-2017-0506</org_study_id>
    <nct_id>NCT03244319</nct_id>
  </id_info>
  <brief_title>Explore the Efficacy and Safety of edoxabaN in Patients After Heart Valve Repair or Bioprosthetic vaLve Replacement (ENAVLE Trial)</brief_title>
  <official_title>Explore the Efficacy and Safety of edoxabaN in Patients After Heart Valve Repair or Bioprosthetic vaLve Replacement (ENAVLE Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yonsei University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yonsei University</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>
      1. objectives: The primary aim of ENAVLE is to explore the efficacy of edoxaban in patients&#xD;
           with post mitral valve repair or bioprosthetic valve implantation&#xD;
&#xD;
        2. Primary / Secondary Endpoint&#xD;
&#xD;
      1) Efficacy Endpoint Evaluation: Occurrence of thromboembolic events and any thrombus at&#xD;
      repaired ring or bioprosthetic valves detected by follow up echocardiography or 3D CT scan&#xD;
&#xD;
      2) Safety Endpoint Evaluation&#xD;
&#xD;
        -  Dysfunction of treated valve caused by thrombosis on echocardiography or 3D CT scan&#xD;
&#xD;
        -  Major or minor bleeding described in safety outcomes&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is an open labeled, parallel group, and randomization study. At 7 days after&#xD;
      mitral valve repair, bioprosthetic MV or AV replacement surgery, warfarin or edoxaban will be&#xD;
      started per oral route. All study patients started to receive bridging therapy with&#xD;
      parenteral anti-coagulant (UFH) according to local practice before switching to warfarin or&#xD;
      edoxaban. Among patients who take warfarin, international normalized ratio will be used to&#xD;
      monitor the effectiveness of the anticoagulant warfarin as usual daily practice. All patients&#xD;
      who are assigned to VKA group, bridging with warfarin and UFH is mandatory until INR reach&#xD;
      therapeutic target range (INR 2-3). Warfarin dose will be adjusted for maintain therapeutic&#xD;
      range (INR 2-3) during follow up period. Patients who are randomly assigned to edoxaban group&#xD;
      will be received 60mg qd or 30mg qd ( creatinine clearance 30-49ml/min, body weight &lt;60kg or&#xD;
      concomitant use of certain P-glycoprotein inhibitors). Both drugs will be maintained for 3&#xD;
      months. During study period, all patients will be carefully monitored for thromboembolic&#xD;
      events including valve dysfunction, and stroke or bleeding complication. At 3 months after&#xD;
      surgery, 3 dimensional CT scan and echocardiography will be performed for detecting valvular&#xD;
      dysfunction, any thrombus or bleeding in heart &amp; lung.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 1, 2017</start_date>
  <completion_date type="Actual">September 30, 2019</completion_date>
  <primary_completion_date type="Actual">September 30, 2019</primary_completion_date>
  <phase>Phase 3</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Occurrence of thromboembolic event</measure>
    <time_frame>12 weeks</time_frame>
    <description>Occurrence of thromboembolic events and any thrombus at repaired ring or bioprosthetic valves detected by follow up echocardiography or 3D CT scan</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Dysfunction of treated valve</measure>
    <time_frame>12 weeks</time_frame>
    <description>Dysfunction of treated valve caused by thrombosis on echocardiography or 3D CT scan</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">220</enrollment>
  <condition>MV(Mitral Valve) Repair</condition>
  <arm_group>
    <arm_group_label>Edoxaban</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Warfarin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Edoxaban</intervention_name>
    <description>Patients who are randomly assigned to edoxaban group will be received 60mg qd or 30mg qd (creatinine clearance 30-49ml/min, body weight &lt;60kg or concomitant use of certain P-glycoprotein inhibitors).</description>
    <arm_group_label>Edoxaban</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Warfarin</intervention_name>
    <description>All patients who are assigned to VKA group, bridging with warfarin and UFH is mandatory until INR reach therapeutic target range (INR 2-3). Warfarin dose will be adjusted for maintain therapeutic range (INR 2-3) during follow up period.</description>
    <arm_group_label>Warfarin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>parenteral anti-coagulant (UFH)</intervention_name>
    <description>parenteral anti-coagulant (UFH)</description>
    <arm_group_label>Warfarin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged 20-85 years with&#xD;
&#xD;
          -  MV repair or Bioprosthetic MV or AV replacement&#xD;
&#xD;
          -  Patients with written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous mechanical prosthetic heart valve replacement&#xD;
&#xD;
          -  Patients who underwent TAVI&#xD;
&#xD;
          -  Concomitant bioprosthetic valve replacement of mechanical tricuspid or pulmonary&#xD;
             replacement at the time of the index valve replacement surgery&#xD;
&#xD;
          -  Clinically relevant paravalvular leaks&#xD;
&#xD;
          -  Previous history of endocarditis&#xD;
&#xD;
          -  Complex congenital heart abnormality&#xD;
&#xD;
          -  Acute coronary syndrome within one month&#xD;
&#xD;
          -  Uncontrolled hypertension&#xD;
&#xD;
          -  Previous history of hemorrhagic stroke&#xD;
&#xD;
          -  At high risk for bleeding&#xD;
&#xD;
          -  Active hepatitis or liver dysfunction (AST/ALT&gt; 3times of upper normal limits)&#xD;
&#xD;
          -  Creatinine clearance &lt; 30ml/min&#xD;
&#xD;
          -  Patients with a clear indication for long-term dual antiplatelet therapy&#xD;
&#xD;
          -  Malignancy or radiation therapy within one month&#xD;
&#xD;
          -  Treatment with selected drugs that my interact with edoxaban (specific P-gp&#xD;
             inhibitors, ie. verapamil, quinidine; the short-term use of azithromycin,&#xD;
             clarithromycin, erythromycin, oral itraconazole, oral ketoconazole)&#xD;
&#xD;
          -  At of pregnancy or breastfeeding&#xD;
&#xD;
          -  Known allergy to warfarin or edoxaban&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>August 6, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>December 27, 2019</last_update_submitted>
  <last_update_submitted_qc>December 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Warfarin</mesh_term>
    <mesh_term>Edoxaban</mesh_term>
    <mesh_term>Anticoagulants</mesh_term>
    <mesh_term>Coagulants</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03244319
org study id: 4-2017-0506
nct id: NCT03244319
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
1. objectives: The primary aim of ENAVLE is to explore the efficacy of edoxaban in patients
           with post mitral valve repair or bioprosthetic valve implantation

        2. Primary / Secondary Endpoint

      1) Efficacy Endpoint Evaluation: Occurrence of thromboembolic events and any thrombus at
      repaired ring or bioprosthetic valves detected by follow up echocardiography or 3D CT scan

      2) Safety Endpoint Evaluation

        -  Dysfunction of treated valve caused by thrombosis on echocardiography or 3D CT scan

        -  Major or minor bleeding described in safety outcomes
This study is an open labeled, parallel group, and randomization study. At 7 days after
      mitral valve repair, bioprosthetic MV or AV replacement surgery, warfarin or edoxaban will be
      started per oral route. All study patients started to receive bridging therapy with
      parenteral anti-coagulant (UFH) according to local practice before switching to warfarin or
      edoxaban. Among patients who take warfarin, international normalized ratio will be used to
      monitor the effectiveness of the anticoagulant warfarin as usual daily practice. All patients
      who are assigned to VKA group, bridging with warfarin and UFH is mandatory until INR reach
      therapeutic target range (INR 2-3). Warfarin dose will be adjusted for maintain therapeutic
      range (INR 2-3) during follow up period. Patients who are randomly assigned to edoxaban group
      will be received 60mg qd or 30mg qd ( creatinine clearance 30-49ml/min, body weight <60kg or
      concomitant use of certain P-glycoprotein inhibitors). Both drugs will be maintained for 3
      months. During study period, all patients will be carefully monitored for thromboembolic
      events including valve dysfunction, and stroke or bleeding complication. At 3 months after
      surgery, 3 dimensional CT scan and echocardiography will be performed for detecting valvular
      dysfunction, any thrombus or bleeding in heart & lung.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurrence of thromboembolic event
time frame: 12 weeks
description: Occurrence of thromboembolic events and any thrombus at repaired ring or bioprosthetic valves detected by follow up echocardiography or 3D CT scan
measure: Dysfunction of treated valve
time frame: 12 weeks
description: Dysfunction of treated valve caused by thrombosis on echocardiography or 3D CT scan
arm group label: Edoxaban
arm group type: Experimental
arm group label: Warfarin
arm group type: Active Comparator
intervention type: Drug
intervention name: Edoxaban
description: Patients who are randomly assigned to edoxaban group will be received 60mg qd or 30mg qd (creatinine clearance 30-49ml/min, body weight <60kg or concomitant use of certain P-glycoprotein inhibitors).
arm group label: Edoxaban
intervention type: Drug
intervention name: Warfarin
description: All patients who are assigned to VKA group, bridging with warfarin and UFH is mandatory until INR reach therapeutic target range (INR 2-3). Warfarin dose will be adjusted for maintain therapeutic range (INR 2-3) during follow up period.
arm group label: Warfarin
intervention type: Drug
intervention name: parenteral anti-coagulant (UFH)
description: parenteral anti-coagulant (UFH)
arm group label: Warfarin
criteria: 
gender: All
minimum age: 20 Years
maximum age: 85 Years
healthy volunteers: No
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Warfarin
mesh term: Edoxaban
mesh term: Anticoagulants
mesh term: Coagulants
sharing ipd: No