<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/NCT04402931</url>
  </required_header>
  <id_info>
    <org_study_id>4993/2019</org_study_id>
    <nct_id>NCT04402931</nct_id>
  </id_info>
  <brief_title>Randomized Trial of Transcatheter Valve-in-Valve vs Redo Surgery for Bioprosthetic Mitral Dysfunction</brief_title>
  <official_title>Randomized Trial of Transcatheter Valve-in-Valve Intervention vs Redo Surgery for the Treatment of Structural Mitral Bioprosthetic Dysfunction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto Dante Pazzanese de Cardiologia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Edwards Lifesciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Instituto Dante Pazzanese de Cardiologia</source>
  <oversight_info>
    <has_dmc>No</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>
      Transcatheter valve-in-valve implantation has emerged as a valid alternative to redo surgery&#xD;
      for patients with surgical bioprosthetic dysfunction. Nowadays, transcatheter, transeptal&#xD;
      mitral valve-in-valve replacement (TsMViV) has been adopted in many centers worldwide. Some&#xD;
      studies report low rates of periprocedural morbidity and mortality and favorable hemodynamic&#xD;
      parameters of valve performance. However, medium and long-term data on TsMViV as compared to&#xD;
      redo surgical mitral valve replacement (rSMVR) is not yet established. Studies of&#xD;
      cost-effectiveness and cost-utility comparing both strategies were also not reported. In&#xD;
      particular, late prosthesis durability and hemodynamic performance after TsMViV are largely&#xD;
      unknown and need to be elucidated before widely indicated, especially among younger and&#xD;
      low-risk surgical candidates with failed mitral bioprostheses.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prospective, randomized, controlled trial of transeptal, transcatheter mitral valve-in-valve&#xD;
      versus redo surgical mitral valve replacement.&#xD;
&#xD;
      After multidisciplinary, heart team discussion, patients meeting inclusion criteria will be&#xD;
      randomized 1:1 to receive either transcatheter, transeptal mitral valve-in-valve replacement&#xD;
      (TsMViV) with the SAPIEN 3 transcatheter heart valve (THV) or redo, mitral valve replacement&#xD;
      with 3 commercially available surgical bioprosthetic valves. A sub-randomization in the&#xD;
      surgical group will define which bioprosthetic valve will be used. Patients will be seen for&#xD;
      follow-up visits at discharge, 30 days, 6 months and annually through 10 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 17, 2020</start_date>
  <completion_date type="Anticipated">December 2031</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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of Major cardiovascular and Cerebrovascular events</measure>
    <time_frame>12 months</time_frame>
    <description>All-cause death; Cardiovascular death; Disabling stroke (neurologist assessment)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of Procedure-related complications</measure>
    <time_frame>30 days</time_frame>
    <description>Major vascular complications;&#xD;
Bleeding and transfusions;&#xD;
Atrial fibrillation;&#xD;
Acute renal failure;&#xD;
Left-ventricular outflow obstruction;&#xD;
Reoperation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Rehospitalization</measure>
    <time_frame>12 months</time_frame>
    <description>Rehospitalization at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Prosthetic Thrombosis</measure>
    <time_frame>3 and 12 months</time_frame>
    <description>Prosthetic thrombosis at 3- and 12 months (as assessed by transesophageal echocardiography and multi-slice tomography).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Structural Valve dysfunction (as assessed by transthoracic echocardiography)</measure>
    <time_frame>10 years</time_frame>
    <description>Structural valve dysfunction assessed annually, up to 10-year follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Bioprosthetic Valve Failure (as assessed by clinical outcomes and echocardiographic evaluations)</measure>
    <time_frame>10 years</time_frame>
    <description>Bioprosthetic valve failure assessed annually, up to 10-year follow-up.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Mitral Prosthetic Valve Stenosis and Regurgitation</condition>
  <arm_group>
    <arm_group_label>Transcatheter Valve-in-Valve Intervention</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Transcatheter Valve-in-Valve Intervention</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Redo Surgery</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Surgical Mitral valve replacement</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Transcatheter Valve-in-Valve Intervention</intervention_name>
    <description>Transcatheter mitral valve-in-valve implantation with SAPIEN 3</description>
    <arm_group_label>Transcatheter Valve-in-Valve Intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Redo Mitral valve surgery</intervention_name>
    <description>Transcatheter Valve-in-Valve Intervention</description>
    <arm_group_label>Redo Surgery</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age&lt;70 years;&#xD;
&#xD;
          -  Symptoms of heart failure NYHA class&gt;ll;&#xD;
&#xD;
          -  Severe mitral bioprosthetic dysfunction (stenosis, regurgitation, mixed) defined by&#xD;
             echocardiography;&#xD;
&#xD;
          -  Heart team (including cardiac surgeon) agree on eligibility including assessment that&#xD;
             transeptal, transcatheter mitral valve replacement (TsMVR) and redo surgical mitral&#xD;
             valve replacement (rSMVR) are appropriate;&#xD;
&#xD;
          -  The study patient or the study patient's legal representative informed of the nature&#xD;
             of the study, agreed to its provisions and provided written informed consent as&#xD;
             approved by the Institutional Review Board (IRB) center;&#xD;
&#xD;
          -  The study patient agreed to comply with all required post- procedure follow-up visits&#xD;
             including annual visits through 10 years and analysis close date visits, which was&#xD;
             conducted as a phone follow-up;&#xD;
&#xD;
          -  Heart team agreed (a priori) on treatment strategy for concomitant coronary disease&#xD;
             (if present);&#xD;
&#xD;
          -  Patient agreed to undergo redo surgical mitral valve replacement (rSMVR) if randomized&#xD;
             to control treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Heart Team assessment of inoperability (including examining cardiac surgeon);&#xD;
&#xD;
          -  Hostile chest;&#xD;
&#xD;
          -  Evidence of an acute myocardial infarction &lt; 1 month (30 days) before the intended&#xD;
             treatment [defined as: Q wave Ml, or non-Q wave Ml with total creatine kinase (CK),&#xD;
             creatine kinase MB isoform (CK-MB) and/or cardiac troponin elevations (WHO&#xD;
             definition)];&#xD;
&#xD;
          -  Concomitant severe valvular disease (aortic, tricuspid or pulmonic) requiring surgical&#xD;
             intervention;&#xD;
&#xD;
          -  Mitral mechanical prosthesis or mitral valve rings;&#xD;
&#xD;
          -  Preexisting mechanical or bioprosthetic valve in other position with dysfunction;&#xD;
&#xD;
          -  Complex coronary artery disease: unprotected left main coronary artery, Syntax score &gt;&#xD;
             32 (in the absence of prior revascularization);&#xD;
&#xD;
          -  Any therapeutic invasive cardiac procedure resulting in a permanent implant that is&#xD;
             performed within 30 days of the index procedure (unless part of planned strategy for&#xD;
             treatment of concomitant coronary artery disease). Implantation of a permanent&#xD;
             pacemaker is not an exclusion criteria;&#xD;
&#xD;
          -  Patients with planned concomitant surgical or transcatheter ablation for atrial&#xD;
             fibrillation;&#xD;
&#xD;
          -  Leukopenia (WBC &lt; 3000 cell/mL), acute anemia (Hgb&lt; 9 g/dL), thrombocytopenia (Pht&lt;&#xD;
             50,000 cell/mL);&#xD;
&#xD;
          -  Hypertrophic cardiomyopathy with or without obstruction (HOCM);&#xD;
&#xD;
          -  Severe ventricular dysfunction with left-ventricular ejection fraction (LVEF) &lt; 20%;&#xD;
&#xD;
          -  Echocardiographic evidence of intracardiac mass, thrombus or vegetation;&#xD;
&#xD;
          -  Active upper gastrointestinal (GI) bleeding within 3 months (90 days) prior to&#xD;
             procedure;&#xD;
&#xD;
          -  A known contraindication or hypersensitivity to all anticoagulation regimens, or&#xD;
             inability to be anticoagulated for the study procedure;&#xD;
&#xD;
          -  Clinically (by neurologist) or neuroimaging confirmed stroke or transient ischemic&#xD;
             attack (TIA) within 3 months (90 days) of the procedure;&#xD;
&#xD;
          -  Renal insufficiency (creatinine &gt; 3.0 mg/dL) and/or renal replacement therapy at the&#xD;
             time of screening;&#xD;
&#xD;
          -  Estimated life expectancy &lt; 24 months (730 days) due to carcinomas, chronic liver&#xD;
             disease, chronic renal disease or chronic end stage pulmonary disease;&#xD;
&#xD;
          -  Currently participating in an investigational drug or another device study;&#xD;
&#xD;
          -  Active bacterial endocarditis within 6 months (180 days) of procedure;&#xD;
&#xD;
          -  Patient refuses redo mitral valve replacement surgery.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dimytri Siqueira, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instituto Dante Pazzanese de Cardiologia</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Dimytri Siqueira, MD, PhD</last_name>
    <phone>+5511994516856</phone>
    <email>dimytrisiqueira@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Renata Viana, MD</last_name>
    <phone>+551150856325</phone>
    <email>rviana@dantepazzanese.org.br</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Instituto Dante Pazzanese de Cardiologia</name>
      <address>
        <city>São Paulo</city>
        <zip>04012909</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dimytri A Siqueira, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>DImytri A Siqueira, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alexandre A Abizaid, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Auristela A Ramos, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Fausto Feres, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 9, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>May 21, 2020</last_update_submitted>
  <last_update_submitted_qc>May 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Instituto Dante Pazzanese de Cardiologia</investigator_affiliation>
    <investigator_full_name>DIMYTRI ALEXANDRE DE ALVIM SIQUEIRA</investigator_full_name>
    <investigator_title>Chief, Interventions in Acquired Valvular Heart Disease</investigator_title>
  </responsible_party>
  <keyword>Mitral Prosthetic valve dysfunction</keyword>
  <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/NCT04402931
org study id: 4993/2019
nct id: NCT04402931
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Transcatheter valve-in-valve implantation has emerged as a valid alternative to redo surgery
      for patients with surgical bioprosthetic dysfunction. Nowadays, transcatheter, transeptal
      mitral valve-in-valve replacement (TsMViV) has been adopted in many centers worldwide. Some
      studies report low rates of periprocedural morbidity and mortality and favorable hemodynamic
      parameters of valve performance. However, medium and long-term data on TsMViV as compared to
      redo surgical mitral valve replacement (rSMVR) is not yet established. Studies of
      cost-effectiveness and cost-utility comparing both strategies were also not reported. In
      particular, late prosthesis durability and hemodynamic performance after TsMViV are largely
      unknown and need to be elucidated before widely indicated, especially among younger and
      low-risk surgical candidates with failed mitral bioprostheses.
Prospective, randomized, controlled trial of transeptal, transcatheter mitral valve-in-valve
      versus redo surgical mitral valve replacement.

      After multidisciplinary, heart team discussion, patients meeting inclusion criteria will be
      randomized 1:1 to receive either transcatheter, transeptal mitral valve-in-valve replacement
      (TsMViV) with the SAPIEN 3 transcatheter heart valve (THV) or redo, mitral valve replacement
      with 3 commercially available surgical bioprosthetic valves. A sub-randomization in the
      surgical group will define which bioprosthetic valve will be used. Patients will be seen for
      follow-up visits at discharge, 30 days, 6 months and annually through 10 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of Major cardiovascular and Cerebrovascular events
time frame: 12 months
description: All-cause death; Cardiovascular death; Disabling stroke (neurologist assessment)
measure: Rate of Procedure-related complications
time frame: 30 days
description: Major vascular complications;
Bleeding and transfusions;
Atrial fibrillation;
Acute renal failure;
Left-ventricular outflow obstruction;
Reoperation
measure: Rate of Rehospitalization
time frame: 12 months
description: Rehospitalization at 12 months
measure: Rate of Prosthetic Thrombosis
time frame: 3 and 12 months
description: Prosthetic thrombosis at 3- and 12 months (as assessed by transesophageal echocardiography and multi-slice tomography).
measure: Rate of Structural Valve dysfunction (as assessed by transthoracic echocardiography)
time frame: 10 years
description: Structural valve dysfunction assessed annually, up to 10-year follow-up.
measure: Rate of Bioprosthetic Valve Failure (as assessed by clinical outcomes and echocardiographic evaluations)
time frame: 10 years
description: Bioprosthetic valve failure assessed annually, up to 10-year follow-up.
arm group label: Transcatheter Valve-in-Valve Intervention
arm group type: Other
description: Transcatheter Valve-in-Valve Intervention
arm group label: Redo Surgery
arm group type: Other
description: Surgical Mitral valve replacement
intervention type: Procedure
intervention name: Transcatheter Valve-in-Valve Intervention
description: Transcatheter mitral valve-in-valve implantation with SAPIEN 3
arm group label: Transcatheter Valve-in-Valve Intervention
intervention type: Procedure
intervention name: Redo Mitral valve surgery
description: Transcatheter Valve-in-Valve Intervention
arm group label: Redo Surgery
criteria: 
gender: All
minimum age: N/A
maximum age: 70 Years
healthy volunteers: No
last name: Dimytri Siqueira, MD, PhD
role: Principal Investigator
affiliation: Instituto Dante Pazzanese de Cardiologia
last name: Dimytri Siqueira, MD, PhD
phone: +5511994516856
email: dimytrisiqueira@gmail.com
last name: Renata Viana, MD
phone: +551150856325
email: rviana@dantepazzanese.org.br
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Instituto Dante Pazzanese de Cardiologia
investigator full name: DIMYTRI ALEXANDRE DE ALVIM SIQUEIRA
investigator title: Chief, Interventions in Acquired Valvular Heart Disease
sharing ipd: No