<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/NCT03807921</url>
  </required_header>
  <id_info>
    <org_study_id>ANTIPRO</org_study_id>
    <nct_id>NCT03807921</nct_id>
  </id_info>
  <brief_title>Anticoagulation for Aortic Bioprosthesis (ANTIPRO)</brief_title>
  <official_title>Randomized Control Study of Anticoagulation With Warfarin Por Patients With Aortic Bioprosthesis vs Aspirin Only</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto Nacional de Cirugia Cardiaca, Uruguay</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Universidad de la Republica</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Instituto Nacional de Cirugia Cardiaca, Uruguay</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>
      This study evaluates the clinical and hemodynamic outcome in patients after aortic valve&#xD;
      replacement. Half of the patients will receive warfarin + aspirin and the other half will&#xD;
      receive only aspirin. The investigators will focus mainly on early bioprosthesis&#xD;
      degeneration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aortic bioprosthesis have the advantage that they do not require life-long anticoagulation.&#xD;
      Current guidelines support the use of aspirin (AAS) 100 mg as a class I indication.&#xD;
&#xD;
      Current evidence, mainly derived from transaortic valve implantation (TAVI) patients, have&#xD;
      shown that aortic bioprosthesis suffer subclinical thrombosis which may explain the increase&#xD;
      in gradient and bioprosthetic degeneration. Anticoagulation in this cases improve leaflet&#xD;
      mobility and decrease in gradient. Evidence supporting early anticoagulation in patients with&#xD;
      aortic bioprosthesis is not as strong as in the case of mitral bioprosthesis. Nonetheless,&#xD;
      current American Heart Association/American College of Cardiology (AHA/ACC) guidelines&#xD;
      recommend (IIa) the use of warfarin for at least 3 months after aortic valve replacement.&#xD;
&#xD;
      The aim is to conduct a single blinded (echocardiographist) randomized control study in&#xD;
      patients who receive an aortic bioprosthesis. Comparison will be performed between the use of&#xD;
      warfarin + aspirin vs aspirin alone. Duration of anticoagulation will be for 3 months and&#xD;
      patients follow-up for 1 year. Clinical and echocardiographic evaluation will be performed in&#xD;
      every patients. Some patients will undergo Positron Emission Tomography (PET-Scan).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Actual">December 31, 2019</completion_date>
  <primary_completion_date type="Actual">December 30, 2019</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>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Transprosthetic aortic gradient</measure>
    <time_frame>3 months and 1 year</time_frame>
    <description>Change in Transprosthetic mean gradient</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in New York Heart Association (NYHA) class</measure>
    <time_frame>1 year</time_frame>
    <description>NYHA class</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Major bleeding</measure>
    <time_frame>3 months and 1 year</time_frame>
    <description>number of patients admitted due to Genitourinary (GU) or Gastrointestinal (GI) bleeding, pericardial tamponade, pleural effusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Embolic events</measure>
    <time_frame>3 months and 1 year</time_frame>
    <description>Number of patients with cerebral and peripheral ischemic events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prosthetic leak</measure>
    <time_frame>3 months and 1 year</time_frame>
    <description>Change in severity of prosthetic and paraprosthetic leakage</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">140</enrollment>
  <condition>Aortic Valve Stenosis</condition>
  <condition>Aortic Valve Disease</condition>
  <condition>Aortic Valve Insufficiency</condition>
  <condition>Aortic Valve Regurgitation</condition>
  <arm_group>
    <arm_group_label>Warfarin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Warfarin will be started 48-72h after aortic valve replacement. Dose will be 5 mg daily in order to obtain an Internation normal ratio (INR) of 2-3. Warfarin treatment will continue for 3 months.&#xD;
Aspirin will be administered 100 mg daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aspirin only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Aspirin will be started 48-72h after aortic valve replacement. Dose will be 100 mg daily. Patients who undergo coronary artery revascularization will receive 325 mg daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Warfarin</intervention_name>
    <description>Oral anticoagulation</description>
    <arm_group_label>Warfarin</arm_group_label>
    <other_name>Choice</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin</intervention_name>
    <description>Antiplatelet treatment</description>
    <arm_group_label>Aspirin only</arm_group_label>
    <arm_group_label>Warfarin</arm_group_label>
    <other_name>AAS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with indication of aortic valve replacement with porcine bioprosthesis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concomitant mitral valve replacement&#xD;
&#xD;
          -  Previous atrial fibrillation&#xD;
&#xD;
          -  Previous use oral anticoagulation&#xD;
&#xD;
          -  Contraindication for the use of oral anticoagulation (high risk of bleeding,&#xD;
             intolerance, allergy)&#xD;
&#xD;
          -  Jehovah witness&#xD;
&#xD;
          -  Platelet count below 90,000.&#xD;
&#xD;
          -  Liver disease&#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>Victor Dayan, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instituto Nacional de Cirugia Cardiaca</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Diego Freire, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centro Cardiovascular Universitario</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centro Cardiovascular Universitario</name>
      <address>
        <city>Montevideo</city>
        <country>Uruguay</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Nacional de Cirugia Cardiaca</name>
      <address>
        <city>Montevideo</city>
        <country>Uruguay</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Uruguay</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 17, 2019</study_first_posted>
  <last_update_submitted>February 21, 2022</last_update_submitted>
  <last_update_submitted_qc>February 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Instituto Nacional de Cirugia Cardiaca, Uruguay</investigator_affiliation>
    <investigator_full_name>Victor Dayan</investigator_full_name>
    <investigator_title>Cardiac Surgeon</investigator_title>
  </responsible_party>
  <keyword>aortic valve replacement</keyword>
  <keyword>bioprosthesis</keyword>
  <keyword>anticoagulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aortic Valve Stenosis</mesh_term>
    <mesh_term>Aortic Valve Disease</mesh_term>
    <mesh_term>Aortic Valve Insufficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Warfarin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Study protocol.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>From January 2019</ipd_time_frame>
    <ipd_access_criteria>Protocol will be shared by email. Investigators interested should send email to the PI who will evaluate the solicitude.</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/NCT03807921
org study id: ANTIPRO
nct id: NCT03807921
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study evaluates the clinical and hemodynamic outcome in patients after aortic valve
      replacement. Half of the patients will receive warfarin + aspirin and the other half will
      receive only aspirin. The investigators will focus mainly on early bioprosthesis
      degeneration.
Aortic bioprosthesis have the advantage that they do not require life-long anticoagulation.
      Current guidelines support the use of aspirin (AAS) 100 mg as a class I indication.

      Current evidence, mainly derived from transaortic valve implantation (TAVI) patients, have
      shown that aortic bioprosthesis suffer subclinical thrombosis which may explain the increase
      in gradient and bioprosthetic degeneration. Anticoagulation in this cases improve leaflet
      mobility and decrease in gradient. Evidence supporting early anticoagulation in patients with
      aortic bioprosthesis is not as strong as in the case of mitral bioprosthesis. Nonetheless,
      current American Heart Association/American College of Cardiology (AHA/ACC) guidelines
      recommend (IIa) the use of warfarin for at least 3 months after aortic valve replacement.

      The aim is to conduct a single blinded (echocardiographist) randomized control study in
      patients who receive an aortic bioprosthesis. Comparison will be performed between the use of
      warfarin + aspirin vs aspirin alone. Duration of anticoagulation will be for 3 months and
      patients follow-up for 1 year. Clinical and echocardiographic evaluation will be performed in
      every patients. Some patients will undergo Positron Emission Tomography (PET-Scan).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Transprosthetic aortic gradient
time frame: 3 months and 1 year
description: Change in Transprosthetic mean gradient
measure: Change in New York Heart Association (NYHA) class
time frame: 1 year
description: NYHA class
measure: Major bleeding
time frame: 3 months and 1 year
description: number of patients admitted due to Genitourinary (GU) or Gastrointestinal (GI) bleeding, pericardial tamponade, pleural effusion
measure: Embolic events
time frame: 3 months and 1 year
description: Number of patients with cerebral and peripheral ischemic events
measure: Prosthetic leak
time frame: 3 months and 1 year
description: Change in severity of prosthetic and paraprosthetic leakage
arm group label: Warfarin
arm group type: Experimental
description: Warfarin will be started 48-72h after aortic valve replacement. Dose will be 5 mg daily in order to obtain an Internation normal ratio (INR) of 2-3. Warfarin treatment will continue for 3 months.
Aspirin will be administered 100 mg daily.
arm group label: Aspirin only
arm group type: Active Comparator
description: Aspirin will be started 48-72h after aortic valve replacement. Dose will be 100 mg daily. Patients who undergo coronary artery revascularization will receive 325 mg daily.
intervention type: Drug
intervention name: Warfarin
description: Oral anticoagulation
arm group label: Warfarin
other name: Choice
intervention type: Drug
intervention name: Aspirin
description: Antiplatelet treatment
arm group label: Aspirin only
arm group label: Warfarin
other name: AAS
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Victor Dayan, MD, PhD
role: Principal Investigator
affiliation: Instituto Nacional de Cirugia Cardiaca
last name: Diego Freire, MD
role: Principal Investigator
affiliation: Centro Cardiovascular Universitario
facility: 
facility: 
country: Uruguay
responsible party type: Principal Investigator
investigator affiliation: Instituto Nacional de Cirugia Cardiaca, Uruguay
investigator full name: Victor Dayan
investigator title: Cardiac Surgeon
mesh term: Aortic Valve Stenosis
mesh term: Aortic Valve Disease
mesh term: Aortic Valve Insufficiency
mesh term: Aspirin
mesh term: Warfarin
sharing ipd: Yes
ipd description: Study protocol.
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd time frame: From January 2019
ipd access criteria: Protocol will be shared by email. Investigators interested should send email to the PI who will evaluate the solicitude.