<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/NCT02974881</url>
  </required_header>
  <id_info>
    <org_study_id>HL-2016-01</org_study_id>
    <nct_id>NCT02974881</nct_id>
  </id_info>
  <brief_title>HighLife™ Transcatheter Mitral Valve Replacement System Study</brief_title>
  <official_title>HighLife™ Transcatheter Mitral Valve Replacement System for Severe Mitral Regurgitation in Patients at High Surgical Risk</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>HighLife SAS</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>MedPass International</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>HighLife SAS</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>
      Multicenter feasibility study of the HighLife™ TMVR system.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an exploratory clinical study designed to evaluate the feasibility, safety and&#xD;
      performance of the Highlife TMVR System in a population of patients with severe symptomatic&#xD;
      mitral regurgitation, who are not suitable for surgical or approved percutaneous treatments&#xD;
      according to the judgement of the Heart Team. The data gathered in this study will allow to&#xD;
      evaluate the feasibility of mitral replacement using the HighLife™ TMVR system and&#xD;
      characterize the safety and performance profile of the HighLife™ TMVR System.&#xD;
&#xD;
      All patients will be followed periodically up to 12 months after the intervention and long&#xD;
      term safety and performance will be collected annually up to 5 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 20, 2017</start_date>
  <completion_date type="Anticipated">December 15, 2023</completion_date>
  <primary_completion_date type="Actual">November 18, 2018</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>Freedom of major adverse events</measure>
    <time_frame>at 30 days post procedure</time_frame>
    <description>including:&#xD;
All-cause mortality&#xD;
Myocardial infarction or coronary ischemia requiring PCI or CABG&#xD;
Major stroke&#xD;
Life-threatening bleeding (MVARC scale)&#xD;
Major access and vascular complications&#xD;
Stage 2 or 3 acute kidney injury (includes dialysis)&#xD;
Any valve-related dysfunction, migration, thrombosis, or other complication requiring surgery or repeat intervention&#xD;
Severe hypotension, heart failure or respiratory failure requiring intravenous pressors or invasive or mechanical heart failure treatments such as ultrafiltration or hemodynamic assist devices, including intra-aortic balloon pumps or left ventricular or biventricular assist devices, or prolonged intubation for ≥ 48H</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Continued intended performance of the HighLife™ bioprosthesis</measure>
    <time_frame>at 30 days post procedure</time_frame>
    <description>defined as the reduction of mitral regurgitation (MR) to either optimal (0+ to trace) or acceptable (reduced by at least 1 grade from baseline with no more than 2+ MR) without significant mitral stenosis (post-procedure EOA ≥ 1.5 cm2 with a transmitral gradient &lt; 5mmHg) and with no greater than mild (1+) paravalvular MR (and without associated hemolysis)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Technical success</measure>
    <time_frame>immediately after procedure</time_frame>
    <description>defined as alive patient at exit from procedure room, with all of the following:&#xD;
Successful access, delivery and retrieval of the HighLife delivery systems&#xD;
Deployment and correct positioning of the HighLife bioprosthesis&#xD;
Freedom of additional emergency surgery or re-intervention related to the device or access procedure</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Device Success (per MVARC definitions)</measure>
    <time_frame>At 30 days, 6 months and 12 months post procedure</time_frame>
    <description>per MVARC definition</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Procedure Success</measure>
    <time_frame>At 30 days, 6 months and 12 months post procedure</time_frame>
    <description>per MVARC definition</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Success</measure>
    <time_frame>At 30 days, 6 months and 12 months post procedure</time_frame>
    <description>per MVARC definition</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemodynamic Performance vs. Baseline</measure>
    <time_frame>At 7 days, 30 days, at 6 months and 12 months and at 2, 3, 4 and 5 years</time_frame>
    <description>Echocardiographic evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional Improvement vs. Baseline</measure>
    <time_frame>At 30 days, 6 months and 12 months</time_frame>
    <description>New York Heart Association Class 6-Minute Walk Test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Improvement vs. Baseline</measure>
    <time_frame>At 6 months and 12 months</time_frame>
    <description>Kansas City Cardiomyopathy Questionnaire</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Mitral Valve Regurgitation</condition>
  <condition>Mitral Valve Insufficiency</condition>
  <arm_group>
    <arm_group_label>transcatheter mitral valve replacement</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HighLife TMVR System is a novel and innovative approach developed as an alternative treatment for severe MR when medical treatment is maximal and surgical interventions not possible or at high risk. The HighLife TMVR system is composed of a Transcatheter Mitral Valve (TMV), a sub-annular implant (SAI), and their delivery systems and loading tools. The HighLife Valve is a 31 mm mitral bioprosthesis made of a self-expanding Nitinol frame covered with polyester graft and supporting bovine pericardium leaflets. The bioprosthesis is used in conjunction with the Sub-Annular Implant (SAI).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcatheter Mitral Valve Replacement</intervention_name>
    <description>Minimally invasive transcatheter mitral valve implantation using the HighLife™ TMVR system</description>
    <arm_group_label>transcatheter mitral valve replacement</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Severe mitral regurgitation&#xD;
&#xD;
          -  New York Heart Association (NYHA) Functional Class II, III or ambulatory IV.&#xD;
&#xD;
          -  Patient is under maximally tolerated GDMT (incl. CRT) for at least 3 months&#xD;
&#xD;
          -  Multidisciplinary Heart Team consensus that the patient is inoperable or at high-risk&#xD;
             for surgical repair/replacement due to significant co-morbid conditions&#xD;
&#xD;
          -  Multidisciplinary Heart Team consensus that the patient is not a suitable candidate&#xD;
             for other approved percutaneous repair therapy due to anatomical or medical conditions&#xD;
&#xD;
          -  Patient meets the anatomical criteria for HighLife valve sizing as determined by CT&#xD;
             and TEE&#xD;
&#xD;
        Main Exclusion Criteria:&#xD;
&#xD;
          -  Mitral stenosis&#xD;
&#xD;
          -  Rheumatic valve disease&#xD;
&#xD;
          -  Severe calcifications of the mitral annulus and/or mitral leaflets&#xD;
&#xD;
          -  Prior surgical or interventional treatment of the mitral valve&#xD;
&#xD;
          -  Unsuitable anatomy for the transapical access&#xD;
&#xD;
          -  Unsuitable anatomy of the aorta and ilio-femoral vessels for the transfemoral access&#xD;
&#xD;
          -  Untreated clinically significant coronary artery disease requiring revascularization&#xD;
&#xD;
          -  LVEF &lt; 30%&#xD;
&#xD;
          -  LVEDD &gt; 70mm&#xD;
&#xD;
          -  Echocardiographic evidence of intracardiac mass, thrombus or vegetation&#xD;
&#xD;
          -  Hypertrophic Obstructive Cardiomyopathy (HOCM)&#xD;
&#xD;
          -  Any surgical or interventional procedure (including PCI) done in the past 30 days&#xD;
             prior to procedure&#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>Jean-Philippe Collet, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Groupe Hospitalier Pitié-Salpétrière Institut de Cardiologie</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHRU Lille</name>
      <address>
        <city>Lille</city>
        <zip>59000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Privé Jacques Cartier</name>
      <address>
        <city>Massy</city>
        <zip>91300</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nantes</name>
      <address>
        <city>Nantes</city>
        <zip>44000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Groupe Hospitalier Pitié-Salpétrière Institut de Cardiologie</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Rennes Pontchaillou</name>
      <address>
        <city>Rennes</city>
        <zip>35000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Toulouse Rangueil</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum</name>
      <address>
        <city>Bonn</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitäres Herzzentrum Hamburg GmbH (UHZ)</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Herzzentrum Leipzig</name>
      <address>
        <city>Leipzig</city>
        <zip>04289</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Deutsches Herzzentrum München des Freistaates Bayern</name>
      <address>
        <city>Munich</city>
        <zip>80636</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Germany</country>
  </location_countries>
  <removed_countries>
    <country>Italy</country>
  </removed_countries>
  <reference>
    <citation>Lange R, Piazza N. HighLife transcatheter mitral valve replacement. EuroIntervention. 2016 Sep 18;12(Y):Y81-3. doi: 10.4244/EIJV12SYA22. No abstract available.</citation>
    <PMID>27640044</PMID>
  </reference>
  <reference>
    <citation>Stone GW, Adams DH, Abraham WT, Kappetein AP, Genereux P, Vranckx P, Mehran R, Kuck KH, Leon MB, Piazza N, Head SJ, Filippatos G, Vahanian AS; Mitral Valve Academic Research Consortium (MVARC). Clinical Trial Design Principles and Endpoint Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint Definitions: A Consensus Document From the Mitral Valve Academic Research Consortium. J Am Coll Cardiol. 2015 Jul 21;66(3):308-321. doi: 10.1016/j.jacc.2015.05.049.</citation>
    <PMID>26184623</PMID>
  </reference>
  <reference>
    <citation>Barbanti M, Piazza N, Mangiafico S, Buithieu J, Bleiziffer S, Ronsivalle G, Scandura S, Giuffrida A, Popolo Rubbio A, Mazzamuto M, Sgroi C, Lange R, Tamburino C. Transcatheter Mitral Valve Implantation Using the HighLife System. JACC Cardiovasc Interv. 2017 Aug 28;10(16):1662-1670. doi: 10.1016/j.jcin.2017.06.046.</citation>
    <PMID>28838477</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>November 11, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>September 13, 2022</last_update_submitted>
  <last_update_submitted_qc>September 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2022</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>Mitral Valve Insufficiency</mesh_term>
  </condition_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/NCT02974881
org study id: HL-2016-01
nct id: NCT02974881
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Multicenter feasibility study of the HighLife™ TMVR system.
This is an exploratory clinical study designed to evaluate the feasibility, safety and
      performance of the Highlife TMVR System in a population of patients with severe symptomatic
      mitral regurgitation, who are not suitable for surgical or approved percutaneous treatments
      according to the judgement of the Heart Team. The data gathered in this study will allow to
      evaluate the feasibility of mitral replacement using the HighLife™ TMVR system and
      characterize the safety and performance profile of the HighLife™ TMVR System.

      All patients will be followed periodically up to 12 months after the intervention and long
      term safety and performance will be collected annually up to 5 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Freedom of major adverse events
time frame: at 30 days post procedure
description: including:
All-cause mortality
Myocardial infarction or coronary ischemia requiring PCI or CABG
Major stroke
Life-threatening bleeding (MVARC scale)
Major access and vascular complications
Stage 2 or 3 acute kidney injury (includes dialysis)
Any valve-related dysfunction, migration, thrombosis, or other complication requiring surgery or repeat intervention
Severe hypotension, heart failure or respiratory failure requiring intravenous pressors or invasive or mechanical heart failure treatments such as ultrafiltration or hemodynamic assist devices, including intra-aortic balloon pumps or left ventricular or biventricular assist devices, or prolonged intubation for ≥ 48H
measure: Continued intended performance of the HighLife™ bioprosthesis
time frame: at 30 days post procedure
description: defined as the reduction of mitral regurgitation (MR) to either optimal (0+ to trace) or acceptable (reduced by at least 1 grade from baseline with no more than 2+ MR) without significant mitral stenosis (post-procedure EOA ≥ 1.5 cm2 with a transmitral gradient < 5mmHg) and with no greater than mild (1+) paravalvular MR (and without associated hemolysis)
measure: Technical success
time frame: immediately after procedure
description: defined as alive patient at exit from procedure room, with all of the following:
Successful access, delivery and retrieval of the HighLife delivery systems
Deployment and correct positioning of the HighLife bioprosthesis
Freedom of additional emergency surgery or re-intervention related to the device or access procedure
measure: Device Success (per MVARC definitions)
time frame: At 30 days, 6 months and 12 months post procedure
description: per MVARC definition
measure: Procedure Success
time frame: At 30 days, 6 months and 12 months post procedure
description: per MVARC definition
measure: Patient Success
time frame: At 30 days, 6 months and 12 months post procedure
description: per MVARC definition
measure: Hemodynamic Performance vs. Baseline
time frame: At 7 days, 30 days, at 6 months and 12 months and at 2, 3, 4 and 5 years
description: Echocardiographic evaluation
measure: Functional Improvement vs. Baseline
time frame: At 30 days, 6 months and 12 months
description: New York Heart Association Class 6-Minute Walk Test
measure: Quality of Life Improvement vs. Baseline
time frame: At 6 months and 12 months
description: Kansas City Cardiomyopathy Questionnaire
arm group label: transcatheter mitral valve replacement
arm group type: Experimental
description: HighLife TMVR System is a novel and innovative approach developed as an alternative treatment for severe MR when medical treatment is maximal and surgical interventions not possible or at high risk. The HighLife TMVR system is composed of a Transcatheter Mitral Valve (TMV), a sub-annular implant (SAI), and their delivery systems and loading tools. The HighLife Valve is a 31 mm mitral bioprosthesis made of a self-expanding Nitinol frame covered with polyester graft and supporting bovine pericardium leaflets. The bioprosthesis is used in conjunction with the Sub-Annular Implant (SAI).
intervention type: Device
intervention name: Transcatheter Mitral Valve Replacement
description: Minimally invasive transcatheter mitral valve implantation using the HighLife™ TMVR system
arm group label: transcatheter mitral valve replacement
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean-Philippe Collet, MD
role: Principal Investigator
affiliation: Groupe Hospitalier Pitié-Salpétrière Institut de Cardiologie
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
country: Germany
country: Italy
citation: Lange R, Piazza N. HighLife transcatheter mitral valve replacement. EuroIntervention. 2016 Sep 18;12(Y):Y81-3. doi: 10.4244/EIJV12SYA22. No abstract available.
PMID: 27640044
citation: Stone GW, Adams DH, Abraham WT, Kappetein AP, Genereux P, Vranckx P, Mehran R, Kuck KH, Leon MB, Piazza N, Head SJ, Filippatos G, Vahanian AS; Mitral Valve Academic Research Consortium (MVARC). Clinical Trial Design Principles and Endpoint Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint Definitions: A Consensus Document From the Mitral Valve Academic Research Consortium. J Am Coll Cardiol. 2015 Jul 21;66(3):308-321. doi: 10.1016/j.jacc.2015.05.049.
PMID: 26184623
citation: Barbanti M, Piazza N, Mangiafico S, Buithieu J, Bleiziffer S, Ronsivalle G, Scandura S, Giuffrida A, Popolo Rubbio A, Mazzamuto M, Sgroi C, Lange R, Tamburino C. Transcatheter Mitral Valve Implantation Using the HighLife System. JACC Cardiovasc Interv. 2017 Aug 28;10(16):1662-1670. doi: 10.1016/j.jcin.2017.06.046.
PMID: 28838477
responsible party type: Sponsor
mesh term: Mitral Valve Insufficiency