<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/NCT02247128</url>
  </required_header>
  <id_info>
    <org_study_id>POPTAV006</org_study_id>
    <nct_id>NCT02247128</nct_id>
  </id_info>
  <brief_title>Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation</brief_title>
  <acronym>POPular-TAVI</acronym>
  <official_title>Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Antonius Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>St. Antonius Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      At present, a variety of antithrombotic regimens are prescribed in the early postprocedure&#xD;
      period after transcatheter aortic valve implantation (TAVI). Dual antiplatelet therapy (DAPT)&#xD;
      using aspirin and a thienopyridine in the initial period after TAVI is the recommended&#xD;
      strategy; however, mono antiplatelet therapy using aspirin is suggested not to be inferior.&#xD;
      In patients with atrial fibrillation (AF) or another indication for oral anticoagulation&#xD;
      (OAC), no recommendations on best treatment regimen currently exist although triple therapy&#xD;
      (OAC + DAPT) is best avoided due to increased bleeding risk.&#xD;
&#xD;
      We hypothesise that the omission of clopidogrel in the first 3 months after TAVI is safer and&#xD;
      not less beneficial than the addition of clopidogrel to aspirin (cohort A) or OAC (cohort B).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The trial consists of two cohorts:&#xD;
&#xD;
        -  Cohort A, patients without an indication for OAC prior to TAVI.&#xD;
&#xD;
        -  Cohort B, patients with an indication for OAC prior to TAVI (eg. atrial fibrillation,&#xD;
           mechanic mitral valve prosthesis).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2014</start_date>
  <completion_date type="Actual">April 2020</completion_date>
  <primary_completion_date type="Actual">March 2020</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety endpoint</measure>
    <time_frame>1 year</time_frame>
    <description>The primary outcome is a safety endpoint, defined as freedom of all bleeding complications at 1 year after TAVI. The co-primary outcome is the safety endpoint defined as freedom of non-procedure related bleeding complications at 1 year after TAVI. For the classification of bleeding complications the Bleeding Academic Research Consortium Definition for Bleeding (BARC) bleeding classification is primarily used according to the Valve Academic Research Consortium (VARC).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Net-clinical benefit endpoint</measure>
    <time_frame>1 year</time_frame>
    <description>The secondary outcome is a net-clinical benefit endpoint, defined as freedom of the non-hierarchical composite of cardiovascular mortality, non-procedure related bleeding, stroke, or myocardial infarction at 1 year after TAVI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy endpoint</measure>
    <time_frame>1 year</time_frame>
    <description>The co-secondary outcome is an efficacy endpoint, defined as freedom of the non-hierarchical composite of cardiovascular mortality, ischemic stroke, or myocardial infarction at 1 year after TAVI.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pharmacoeconomics endpoint</measure>
    <time_frame>1 year</time_frame>
    <description>Outcome measure is quality-adjusted life years</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">1016</enrollment>
  <condition>Aortic Valve Disease</condition>
  <condition>Myocardial Infarction</condition>
  <condition>Stroke</condition>
  <condition>Bleeding</condition>
  <arm_group>
    <arm_group_label>Aspirin + Clopicogrel (Cohort A)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cohort A: patients will receive clopidogrel (75mg quaque die (qD), 3 months) on top of low-dose aspirin (≤100mg qD, at least 1 year but recommended lifelong). When a patient in Cohort A doesn't already takes aspirin, a loading dose of 300mg will be given within 24 hours prior to TAVI. The loading dose for clopidogrel is 300mg, and will be given within 24 hours prior to TAVI.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aspirin monotherapy (Cohort A)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cohort A: patients will receive low-dose aspirin (≤100mg qD, at least 1 year but recommended lifelong). When a patients doesn't already takes aspirin, a loading dose of 300mg will be given within 24 hours prior to TAVI. It is recommended to omit other antiplatelet therapy (e.g. clopidogrel) at least 5 days prior to the TAVI procedure.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OAC + Clopicogrel (Cohort B)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cohort B: patients will receive clopidogrel (75mg qD, 3 months) on top of OAC (according to its indication). The loading dose for clopidogrel is 300mg, and will be given within 24 hours prior to TAVI. It is recommended to omit other antiplatelet therapy (e.g. aspirin) at least 5 days prior to the TAVI procedure.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OAC monotherapy (Cohort B)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cohort B: patients will receive OAC according to its indication. It is recommended to continue the OAC therapy peri-procedural (International Normalized Ratio aimed at 2.0). It is recommended to omit antiplatelet therapy (e.g. clopidogrel) at least 5 days prior to the TAVI procedure.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin + clopidogrel</intervention_name>
    <arm_group_label>Aspirin + Clopicogrel (Cohort A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin monotherapy</intervention_name>
    <arm_group_label>Aspirin monotherapy (Cohort A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OAC + clopicogrel</intervention_name>
    <arm_group_label>OAC + Clopicogrel (Cohort B)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OAC monotherapy</intervention_name>
    <arm_group_label>OAC monotherapy (Cohort B)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cohort A&#xD;
&#xD;
             1. Patient has provided written informed consent.&#xD;
&#xD;
          -  Cohort B&#xD;
&#xD;
               1. Need for long-term oral anticoagulation;&#xD;
&#xD;
               2. Patient has provided written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cohort A&#xD;
&#xD;
               1. Need for long-term oral anticoagulation;&#xD;
&#xD;
               2. Drug-eluting stent implantation within 3 months prior to TAVI procedure;&#xD;
&#xD;
               3. Bare-metal stent implantation within 1 month prior to TAVI procedure;&#xD;
&#xD;
               4. Allergy or intolerance to aspirin or clopidogrel.&#xD;
&#xD;
          -  Cohort B&#xD;
&#xD;
               1. Drug-eluting stent implantation within 3 months prior to TAVI procedure;&#xD;
&#xD;
               2. Bare-metal stent implantation within 1 month prior to TAVI procedure;&#xD;
&#xD;
               3. Allergy or intolerance to (N)OAC or clopidogrel.&#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>Jurrien M ten Berg, PhD, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Antonius Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pieter R Stella, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Medical Center Utrecht (UMCU)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Algemeen Stedelijk Ziekenhuis</name>
      <address>
        <city>Aalst</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Onze Lieve Vrouwe Ziekenhuis</name>
      <address>
        <city>Aalst</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imelda Ziekenhuis</name>
      <address>
        <city>Bonheiden</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Algemeen Ziekenhuis Sint Jan</name>
      <address>
        <city>Brugge</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ziekenhuis Oost-Limburg</name>
      <address>
        <city>Genk</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Ziekenhuis Leuven</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charles university, Third Faculty of Medicine</name>
      <address>
        <city>Prague</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Institute Surgery Cardiaque Et De Cardiologie Interventionnelle</name>
      <address>
        <city>Luxembourg</city>
        <country>Luxembourg</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Academic Medical Centre (AMC)</name>
      <address>
        <city>Amsterdam</city>
        <state>Noord Holland</state>
        <zip>1105 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Isala Clinics</name>
      <address>
        <city>Zwolle</city>
        <state>Overijssel</state>
        <zip>8011 JW</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Antonius Hospital</name>
      <address>
        <city>Nieuwegein</city>
        <state>Utrecht</state>
        <zip>3435CM</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Haga Ziekenhuis</name>
      <address>
        <city>Den Haag</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medisch Spectrum Twente</name>
      <address>
        <city>Enschede</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Center</name>
      <address>
        <city>Groningen</city>
        <zip>9700 RB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Medisch Centrum Leiden</name>
      <address>
        <city>Leiden</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Academic Hospital</name>
      <address>
        <city>Maastricht</city>
        <zip>6229 HX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Center Utrecht (UMCU)</name>
      <address>
        <city>Utrecht</city>
        <zip>3584 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Czechia</country>
    <country>Luxembourg</country>
    <country>Netherlands</country>
  </location_countries>
  <removed_countries>
    <country>Denmark</country>
    <country>Italy</country>
  </removed_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>September 19, 2014</study_first_submitted>
  <study_first_submitted_qc>September 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 23, 2014</study_first_posted>
  <last_update_submitted>April 29, 2020</last_update_submitted>
  <last_update_submitted_qc>April 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>St. Antonius Hospital</investigator_affiliation>
    <investigator_full_name>J.M. ten Berg</investigator_full_name>
    <investigator_title>Prof. Dr.</investigator_title>
  </responsible_party>
  <keyword>Transcatheter Aortic Valve Implantation (TAVI)</keyword>
  <keyword>Transcatheter Aortic Valve Replacement (TAVR)</keyword>
  <keyword>Aortic Valve Disease</keyword>
  <keyword>Aortic Stenosis</keyword>
  <keyword>Myocardial Infarction</keyword>
  <keyword>Ischemic stroke</keyword>
  <keyword>Bleeding</keyword>
  <keyword>Thrombosis</keyword>
  <keyword>Myocardial Ischemia</keyword>
  <keyword>Heart Diseases</keyword>
  <keyword>Cardiovascular Diseases</keyword>
  <keyword>Vascular Diseases</keyword>
  <keyword>Embolism and Thrombosis</keyword>
  <keyword>Aspirin</keyword>
  <keyword>Clopidogrel</keyword>
  <keyword>Prasugrel</keyword>
  <keyword>Ticagrelor</keyword>
  <keyword>Antithrombotic treatment</keyword>
  <keyword>Oral anticoagulation</keyword>
  <keyword>Warfarin</keyword>
  <keyword>Platelet Aggregation Inhibitors</keyword>
  <keyword>Genetic Testing</keyword>
  <keyword>Cytochrome P450 2C19 (CYP2C19)</keyword>
  <keyword>Prostaglandin-endoperoxide synthase 2(PTGS2)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>Aortic Valve Disease</mesh_term>
    <mesh_term>Infarction</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Clopidogrel</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02247128
org study id: POPTAV006
nct id: NCT02247128
lead sponsor: 
has dmc: Yes
At present, a variety of antithrombotic regimens are prescribed in the early postprocedure
      period after transcatheter aortic valve implantation (TAVI). Dual antiplatelet therapy (DAPT)
      using aspirin and a thienopyridine in the initial period after TAVI is the recommended
      strategy; however, mono antiplatelet therapy using aspirin is suggested not to be inferior.
      In patients with atrial fibrillation (AF) or another indication for oral anticoagulation
      (OAC), no recommendations on best treatment regimen currently exist although triple therapy
      (OAC + DAPT) is best avoided due to increased bleeding risk.

      We hypothesise that the omission of clopidogrel in the first 3 months after TAVI is safer and
      not less beneficial than the addition of clopidogrel to aspirin (cohort A) or OAC (cohort B).
The trial consists of two cohorts:

        -  Cohort A, patients without an indication for OAC prior to TAVI.

        -  Cohort B, patients with an indication for OAC prior to TAVI (eg. atrial fibrillation,
           mechanic mitral valve prosthesis).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Safety endpoint
time frame: 1 year
description: The primary outcome is a safety endpoint, defined as freedom of all bleeding complications at 1 year after TAVI. The co-primary outcome is the safety endpoint defined as freedom of non-procedure related bleeding complications at 1 year after TAVI. For the classification of bleeding complications the Bleeding Academic Research Consortium Definition for Bleeding (BARC) bleeding classification is primarily used according to the Valve Academic Research Consortium (VARC).
measure: Net-clinical benefit endpoint
time frame: 1 year
description: The secondary outcome is a net-clinical benefit endpoint, defined as freedom of the non-hierarchical composite of cardiovascular mortality, non-procedure related bleeding, stroke, or myocardial infarction at 1 year after TAVI.
measure: Efficacy endpoint
time frame: 1 year
description: The co-secondary outcome is an efficacy endpoint, defined as freedom of the non-hierarchical composite of cardiovascular mortality, ischemic stroke, or myocardial infarction at 1 year after TAVI.
measure: Pharmacoeconomics endpoint
time frame: 1 year
description: Outcome measure is quality-adjusted life years
arm group label: Aspirin + Clopicogrel (Cohort A)
arm group type: Active Comparator
description: Cohort A: patients will receive clopidogrel (75mg quaque die (qD), 3 months) on top of low-dose aspirin (≤100mg qD, at least 1 year but recommended lifelong). When a patient in Cohort A doesn't already takes aspirin, a loading dose of 300mg will be given within 24 hours prior to TAVI. The loading dose for clopidogrel is 300mg, and will be given within 24 hours prior to TAVI.
arm group label: Aspirin monotherapy (Cohort A)
arm group type: Active Comparator
description: Cohort A: patients will receive low-dose aspirin (≤100mg qD, at least 1 year but recommended lifelong). When a patients doesn't already takes aspirin, a loading dose of 300mg will be given within 24 hours prior to TAVI. It is recommended to omit other antiplatelet therapy (e.g. clopidogrel) at least 5 days prior to the TAVI procedure.
arm group label: OAC + Clopicogrel (Cohort B)
arm group type: Active Comparator
description: Cohort B: patients will receive clopidogrel (75mg qD, 3 months) on top of OAC (according to its indication). The loading dose for clopidogrel is 300mg, and will be given within 24 hours prior to TAVI. It is recommended to omit other antiplatelet therapy (e.g. aspirin) at least 5 days prior to the TAVI procedure.
arm group label: OAC monotherapy (Cohort B)
arm group type: Active Comparator
description: Cohort B: patients will receive OAC according to its indication. It is recommended to continue the OAC therapy peri-procedural (International Normalized Ratio aimed at 2.0). It is recommended to omit antiplatelet therapy (e.g. clopidogrel) at least 5 days prior to the TAVI procedure.
intervention type: Drug
intervention name: Aspirin + clopidogrel
arm group label: Aspirin + Clopicogrel (Cohort A)
intervention type: Drug
intervention name: Aspirin monotherapy
arm group label: Aspirin monotherapy (Cohort A)
intervention type: Drug
intervention name: OAC + clopicogrel
arm group label: OAC + Clopicogrel (Cohort B)
intervention type: Drug
intervention name: OAC monotherapy
arm group label: OAC monotherapy (Cohort B)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jurrien M ten Berg, PhD, MD
role: Principal Investigator
affiliation: St. Antonius Hospital
last name: Pieter R Stella, MD, PhD
role: Principal Investigator
affiliation: University Medical Center Utrecht (UMCU)
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: Czechia
country: Luxembourg
country: Netherlands
country: Denmark
country: Italy
responsible party type: Principal Investigator
investigator affiliation: St. Antonius Hospital
investigator full name: J.M. ten Berg
investigator title: Prof. Dr.
mesh term: Myocardial Infarction
mesh term: Aortic Valve Disease
mesh term: Infarction
mesh term: Hemorrhage
mesh term: Aspirin
mesh term: Clopidogrel