<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/NCT04489823</url>
  </required_header>
  <id_info>
    <org_study_id>ABT-CIP-10309</org_study_id>
    <nct_id>NCT04489823</nct_id>
  </id_info>
  <brief_title>PARADIGM: Amplatzer Valvular Plug for PVL Closure</brief_title>
  <acronym>PARADIGM</acronym>
  <official_title>PARADIGM PARAvalvular Leak Closure With the Amplatzer Valvular Plug occluDer for Interventional Transcatheter Closure for PVL With Surgical bioloGical and Mechanical Heart Valve</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Abbott Medical Devices</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Abbott Medical Devices</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The Paradigm study is a prospective, multicenter, single arm study to demonstrate the safety&#xD;
      and effectiveness of the AVP III as a treatment for clinically significant PVLs following&#xD;
      surgical implant of a mechanical or biological heart valve implanted in the aortic or mitral&#xD;
      position.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PARADIGM is a prospective, international, multi-center, single arm study to demonstrate the&#xD;
      safety and effectiveness of the AVP III for percutaneous, transcatheter closure of PVLs&#xD;
      occurring after aortic or mitral valve replacement with a surgically-implanted mechanical or&#xD;
      bioprosthetic valve. The study will be conducted at up to 25 clinical sites in the US, EU and&#xD;
      Canada, where a total of 200 subjects with a clinically significant PVL will undergo an AVP&#xD;
      III implant procedure for PVL closure. Pre-procedural Baseline and follow-up assessments at&#xD;
      Discharge, 30 days, 6 months and 1 year will include echocardiography, physical examinations,&#xD;
      lab measurements and questionnaires to assess PVL severity, prosthetic valve function,&#xD;
      hemolytic anemia, heart failure symptoms, and quality of life. Adverse events will be&#xD;
      recorded throughout the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">December 1, 2020</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Paravalvular leak closure success rate (percent of subjects)</measure>
    <time_frame>30 Days</time_frame>
    <description>Defined as AVPIII placement in the intended location without interference with the prosthetic valve or intraprocedural mortality with at least a 2 severity-grade reduction in paravalvular regurgitation at exit from the procedure and freedom from unplanned AVPIII-related transcatheter or surgical reintervention through 30 days post-implant.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Paravalvular Aortic Regurgitation</condition>
  <arm_group>
    <arm_group_label>Paravalvular Leak Closure</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Includes all eligible subjects who undergo an AVP III implant attempt for treatment of significant paravalvular leakage with an echocardiographic severity grade of moderate or higher. This is a single arm study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Amplatzer Valvular Plug III</intervention_name>
    <description>Transcatheter closure of a paravalvular leak using Amplatzer Valvular Plug III</description>
    <arm_group_label>Paravalvular Leak Closure</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject is implanted with a mechanical or biological surgical valve in the aortic or&#xD;
             mitral position&#xD;
&#xD;
          -  Note: Subjects in European countries can only be implanted with a mechanical valve in&#xD;
             the aortic or mitral position&#xD;
&#xD;
          -  Subject has a clinically significant paravalvular leak with a severity grade of&#xD;
             moderate or higher, associated with signs of heart failure and/or hemolysis&#xD;
             necessitating recurring blood transfusions.&#xD;
&#xD;
          -  Subject has one clinically significant PVL defect that can be closed with a single AVP&#xD;
             III as assessed pre-procedurally&#xD;
&#xD;
          -  Subject has provided written informed consent&#xD;
&#xD;
          -  Subject is ≥18 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject has a rocking valve or extreme dehiscence of the prosthetic valve involving&#xD;
             more than 40% of the sewing ring&#xD;
&#xD;
          -  Subject's PVL(s) originates from a transcatheter aortic or mitral valve replacement,&#xD;
             or from rapid deployment or sutureless surgical replacement valves&#xD;
&#xD;
          -  Subject has a prosthetic aortic valve and prosthetic mitral valve which both have a&#xD;
             clinically significant paravalvular leak.&#xD;
&#xD;
          -  Subject who is hemodynamically unstable or who cannot undergo an elective procedure&#xD;
&#xD;
          -  Subject with active endocarditis or other active infection&#xD;
&#xD;
          -  Subject has within the last 6 months a previously documented intracardiac mass,&#xD;
             vegetation, tumor, or thrombus which would interfere with placement of the AVP III&#xD;
&#xD;
          -  Subject has inadequate vasculature for delivery of the AVP III&#xD;
&#xD;
          -  Subject has unsuitable anatomy for PVL closure using the AVP III (such as a PVL&#xD;
             associated with an abscess cavity or a pseudoaneurysmal sac) or anatomy where the AVP&#xD;
             III would interfere with other intracardiac or intravascular structures (such coronary&#xD;
             ostia)&#xD;
&#xD;
          -  Subjects who are unable to receive intraprocedural anticoagulant therapy&#xD;
&#xD;
          -  Pregnant or nursing subjects or subjects who plan pregnancy during the clinical&#xD;
             investigation follow-up period.&#xD;
&#xD;
          -  Presence of other anatomic or comorbid conditions, or other medical, social, or&#xD;
             psychological conditions that, in the investigator's opinion, could limit the&#xD;
             subject's ability to participate in the clinical investigation or to comply with&#xD;
             follow-up requirements, or impact the scientific soundness of the clinical&#xD;
             investigation results.&#xD;
&#xD;
          -  Life expectancy is less than 1 year in the opinion of the Investigator&#xD;
&#xD;
          -  Incapacitated individuals, defined as persons with mental illnesses or handicaps that&#xD;
             impair their ability to provide informed consent, or individuals without legal&#xD;
             authority to provide informed consent.&#xD;
&#xD;
          -  Individual who are currently participating in an investigational drug or device study&#xD;
             that has not reached the primary endpoint or that may confound the results of this&#xD;
             study&#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>Carlos Ruiz, M.D., Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hackensack Meridian Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital - Univ. of Alabama at Birmingham (UAB)</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35249</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent Hospital</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Medical Center</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minneapolis Heart Institute</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Luke's Hospital</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hackensack University Medical Center</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lenox Hill Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Presbyterian Hospital/Cornell University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist Memorial Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Intermountain Medical Center</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carilion Roanoke Memorial Hospital</name>
      <address>
        <city>Roanoke</city>
        <state>Virginia</state>
        <zip>24014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sacred Heart Medical Center</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de Cardiologie de Montreal (Montreal Heart Inst.)</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H1T 1C8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de Cardiologie de Quebec (Hôpital Laval)</name>
      <address>
        <city>Quebec</city>
        <zip>G1V 4G5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Paul's Hospital</name>
      <address>
        <city>Vancouver</city>
        <zip>V6Z 2E8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Raffaele</name>
      <address>
        <city>Milano</city>
        <state>Lombard</state>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Antonius Ziekenhuis</name>
      <address>
        <city>Nieuwegein</city>
        <state>Utrecht</state>
        <zip>3435 CM</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gornoslaskie Centrum Medyczne im.prof. Leszka Gieca</name>
      <address>
        <city>Katowice</city>
        <state>Silesia</state>
        <zip>40-635</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Edinburgh Heart Centre</name>
      <address>
        <city>Edinburgh</city>
        <state>Lothian</state>
        <zip>EH16 4SA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Sussex County Hospital</name>
      <address>
        <city>Brighton</city>
        <state>Soeast</state>
        <zip>BN25BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Papworth Hospital NHS Foundation Trust</name>
      <address>
        <city>Cambridge</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>August 25, 2023</last_update_submitted>
  <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aortic Valve Insufficiency</mesh_term>
  </condition_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/NCT04489823
org study id: ABT-CIP-10309
nct id: NCT04489823
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
The Paradigm study is a prospective, multicenter, single arm study to demonstrate the safety
      and effectiveness of the AVP III as a treatment for clinically significant PVLs following
      surgical implant of a mechanical or biological heart valve implanted in the aortic or mitral
      position.
PARADIGM is a prospective, international, multi-center, single arm study to demonstrate the
      safety and effectiveness of the AVP III for percutaneous, transcatheter closure of PVLs
      occurring after aortic or mitral valve replacement with a surgically-implanted mechanical or
      bioprosthetic valve. The study will be conducted at up to 25 clinical sites in the US, EU and
      Canada, where a total of 200 subjects with a clinically significant PVL will undergo an AVP
      III implant procedure for PVL closure. Pre-procedural Baseline and follow-up assessments at
      Discharge, 30 days, 6 months and 1 year will include echocardiography, physical examinations,
      lab measurements and questionnaires to assess PVL severity, prosthetic valve function,
      hemolytic anemia, heart failure symptoms, and quality of life. Adverse events will be
      recorded throughout the study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Paravalvular leak closure success rate (percent of subjects)
time frame: 30 Days
description: Defined as AVPIII placement in the intended location without interference with the prosthetic valve or intraprocedural mortality with at least a 2 severity-grade reduction in paravalvular regurgitation at exit from the procedure and freedom from unplanned AVPIII-related transcatheter or surgical reintervention through 30 days post-implant.
arm group label: Paravalvular Leak Closure
arm group type: Experimental
description: Includes all eligible subjects who undergo an AVP III implant attempt for treatment of significant paravalvular leakage with an echocardiographic severity grade of moderate or higher. This is a single arm study.
intervention type: Device
intervention name: Amplatzer Valvular Plug III
description: Transcatheter closure of a paravalvular leak using Amplatzer Valvular Plug III
arm group label: Paravalvular Leak Closure
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Carlos Ruiz, M.D., Ph.D
role: Principal Investigator
affiliation: Hackensack Meridian Health
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country: Canada
country: Italy
country: Netherlands
country: Poland
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Aortic Valve Insufficiency
sharing ipd: No