<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/NCT02249000</url>
  </required_header>
  <id_info>
    <org_study_id>C1205</org_study_id>
    <nct_id>NCT02249000</nct_id>
  </id_info>
  <brief_title>BIOVALVE - I / II Clincial Investigation</brief_title>
  <acronym>BIOVALVE</acronym>
  <official_title>Safety and Clinical Performance of the Self-expanding Transcatheter BIOVALVE Prosthesis in Subjects With Severe Symptomatic Aortic Stenosis Suitable for Transfemoral Transcatheter Aortic Valve Implantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biotronik AG</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medstar Health Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Biotronik AG</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      First-in-Human clinical investigation to evaluate the safety and clinical performance of the&#xD;
      BIOVALVE prosthesis in subjects presenting with severe symptomatic aortic valve stenosis,&#xD;
      which are as judged by the heart team, indicated for transfemoral transcatheter aortic valve&#xD;
      implantation&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In a non-randomized, prospective, multi-center clinical investigation, approximately 86&#xD;
      eligible subjects will be enrolled.&#xD;
&#xD;
      Phase 1: BIOVALVE-I feasibility clinical investigation: Approximately 13 eligible subjects&#xD;
      will be enrolled.&#xD;
&#xD;
      Phase 2: BIOVALVE-II pilot clinical investigation: Approximately 73 eligible subjects will be&#xD;
      enrolled.&#xD;
&#xD;
      BIOVALVE-I/II subjects follow the same clinical investigation plan (CIP) in all aspects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Actual">March 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>Early safety at 30 days (Acc. to VARC-2)</measure>
    <time_frame>30 days</time_frame>
    <description>A composite of all-cause mortality, all stroke (disabling/non-disabling), life-threatening bleeding, acute kidney injury stage 2 or 3 (including renal replacement therapy), coronary artery obstruction requiring intervention, major vascular complication and valve-related dysfunction requiring repeat procedure (balloon aortic valvuloplasty (BAV), transcatheter aortic valve implantation (TAVI), or surgical aortic valve replacement (SAVR)).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Combined safety endpoint at 30 days (Acc. to VARC-1)</measure>
    <time_frame>30 days</time_frame>
    <description>A composite of all-cause mortality, major stroke, life-threatening (or disabling) bleeding, acute kidney injury stage 3 (including renal replacement therapy), peri-procedural myocardial infarction, major vascular complication and repeat procedure for valve-related dysfunction (surgical or interventional therapy)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical efficacy after 30 days (Acc. to VARC-2):</measure>
    <time_frame>30 days</time_frame>
    <description>A composite of all-cause mortality, all stroke (disabling and non-disabling), requiring hospitalizations for valve-related symptoms or worsening congestive heart failure, NYHA class III or IV, valve-related dysfunction (mean aortic valve gradient ≥20 mm Hg, effective orifice area (EOA) ≤0.9-1.1 cm2 * and/or Doppler velocity index (DVI) &lt;0.35 m/s, and/or moderate or severe prosthetic valve regurgitation **).&#xD;
* depending on body surface area&#xD;
** refers to VARC-2 definitions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Echocardiograhic (ECHO) parameters</measure>
    <time_frame>Discharge, 30 days, 6 months, 12 months and annually through 5 years</time_frame>
    <description>Effective orifice area (EOA) and effective orifice area index (EOAI) Mean prosthetic valve gradient Prosthetic valve regurgitation (Acc. to VARC-1 and VARC-2)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">86</enrollment>
  <condition>Heart Valve Diseases</condition>
  <condition>Aortic Valve Stenosis</condition>
  <arm_group>
    <arm_group_label>BIOVALVE prosthesis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Transcatheter Aortic Valve Replacement (TAVR)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>BIOVALVE prosthesis</intervention_name>
    <description>Transcatheter Aortic Valve Replacement (TAVR)</description>
    <arm_group_label>BIOVALVE prosthesis</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The subject is ≥65 years&#xD;
&#xD;
          2. The subject has provided written informed consent&#xD;
&#xD;
          3. Subject is willing to participate in the clinical investigation and to comply with all&#xD;
             of the study procedures and follow-up visits&#xD;
&#xD;
          4. NHYA class ≥II&#xD;
&#xD;
          5. High surgical risk: Logistic EuroSCORE-I ≥20% (or equivalence of EuroSCORE-II) or STS&#xD;
             score ≥10% or co-morbidity judged by the heart team (consisting of at least one&#xD;
             interventional cardiologist and one cardiac surgeon) to pose an absolute or relative&#xD;
             contraindication for conventional aortic valve replacement according to VARC-2&#xD;
&#xD;
          6. Severe symptomatic calcific aortic valve stenosis characterized by mean aortic&#xD;
             gradient &gt;40 mm Hg or peak jet velocity &gt;4.0 m/s or effective orifice area (EOA) of&#xD;
             &lt;1.0 cm2 (&lt;0.6 cm2/m2 body surface area)&#xD;
&#xD;
          7. Annulus diameter as determined by multi-slice computed tomography (MSCT) from 23-26 mm&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Trans-esophageal echocardiogram (TEE) is contraindicated&#xD;
&#xD;
          2. Congenital bicuspid or unicuspid valve&#xD;
&#xD;
          3. Left ventricular outflow tract (LVOT) obstruction such as hypertrophic obstructive&#xD;
             cardio myopathy (HOCM) or subject presenting with systolic anterior motion (SAM).&#xD;
             Evidence of intra cardiac mass, thrombus or vegetation&#xD;
&#xD;
          4. Transfemoral access vessel characteristics that would preclude safe placement of a 18&#xD;
             French sheath&#xD;
&#xD;
          5. Vessel and/or anatomical characteristics that would preclude safe delivery of the&#xD;
             BIOVALVE prosthesis to the ascending aorta and/or placement of the prosthesis&#xD;
&#xD;
          6. Anatomical restrictions such as shallow sinuses with heavily calcified leaflets, low&#xD;
             height of coronary ostia, extreme tortuosity of the aortic arch, thoracic (TAA) or&#xD;
             abdominal (AAA) aortic aneurysm, presence of endovascular stent graft&#xD;
&#xD;
          7. Severe mitral regurgitation grade &gt;3&#xD;
&#xD;
          8. Severe mitral stenosis&#xD;
&#xD;
          9. Prosthetic mitral valve&#xD;
&#xD;
         10. Severe left ventricular dysfunction with left ventricular ejection fraction (LVEF)&#xD;
             &lt;20%&#xD;
&#xD;
         11. Hemodynamic instability&#xD;
&#xD;
         12. Percutaneous coronary intervention (PCI) within 30 days prior to index procedure and /&#xD;
             or planned PCI during index procedure&#xD;
&#xD;
         13. Renal insufficiency (creatinine &gt;2.5 mg/dl) or subject under dialysis and/or renal&#xD;
             replacement therapy&#xD;
&#xD;
         14. Any cerebrovascular event or transient ischemic attack (TIA) within 180 days prior to&#xD;
             TAVI procedure&#xD;
&#xD;
         15. Evidence of acute myocardial infarction (defined as ≥2 fold CK level or in absence of&#xD;
             CK a ≥3 fold CKMB level above the upper range limit within ≤30 days prior to TAVI&#xD;
             procedure)&#xD;
&#xD;
         16. Blood dyscrasia defined as: leucopenia (WBC &lt;1000 mm³), thrombocytopenia (platelet&#xD;
             count &lt;50'000 cells/mm³), history of bleeding diathesis requiring blood transfusion&#xD;
&#xD;
         17. Ongoing sepsis or suspected active endocarditis&#xD;
&#xD;
         18. Active peptic ulcer or gastrointestinal bleeding within last 3 months that would&#xD;
             preclude anticoagulation&#xD;
&#xD;
         19. Subject refuses blood transfusion&#xD;
&#xD;
         20. Known hypersensitivity to, or contraindication to nitinol,&#xD;
             anticoagulation/antiplatelet regimes, any other medications required for the procedure&#xD;
             or post-procedure as determined by the heart team, or sensitivity to contrast media&#xD;
             which cannot be adequately pre-medicated&#xD;
&#xD;
         21. Need for emergency TAVI intervention, or other medical, social, or psychological&#xD;
             conditions that in the opinion of the heart team precludes the subjects from&#xD;
             appropriate consent or adherence to protocol required follow-up exams&#xD;
&#xD;
         22. Expectation that subject will not improve despite treatment of aortic stenosis&#xD;
&#xD;
         23. Estimated life expectancy of less than 12 months due to associated non-cardiac&#xD;
             co-morbidities&#xD;
&#xD;
         24. Severe pulmonary hypertension (&gt; 60 mm Hg assessed by continuous wave Doppler, TTE) or&#xD;
             clinical signs of acute severe right ventricular dysfunction&#xD;
&#xD;
         25. Currently participating in another investigational drug or device study where primary&#xD;
             endpoint has not been reached yet&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hendrik Treede, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Universitätsklinikum Halle (Saale), Germany</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ulrich Schaefer, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University Heart Center Hamburg, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ZNA Middelheim</name>
      <address>
        <city>Antwerpen</city>
        <zip>2020</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Städtische Kliniken Neuss - Lukaskrankenhaus</name>
      <address>
        <city>Neuss</city>
        <state>Nordrhein-Westfalen</state>
        <zip>41464</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Segeberger Kliniken</name>
      <address>
        <city>Bad Segeberg</city>
        <state>Schleswig-Holstein</state>
        <zip>23795</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vivantes Klinikum</name>
      <address>
        <city>Berlin</city>
        <zip>10249</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>German Heart Center</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Halle (Saale)</name>
      <address>
        <city>Halle</city>
        <zip>06120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asklepios Klinik St. Georg</name>
      <address>
        <city>Hamburg</city>
        <zip>20099</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Heart Center</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Heart Center</name>
      <address>
        <city>Köln</city>
        <zip>50937</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>Universitätsmedizin Rostock</name>
      <address>
        <city>Rostock</city>
        <zip>18057</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Catharina-Ziekenhuis</name>
      <address>
        <city>Eindhoven</city>
        <zip>5623</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsspital Zürich</name>
      <address>
        <city>Zurich</city>
        <zip>8091</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Germany</country>
    <country>Netherlands</country>
    <country>Switzerland</country>
  </location_countries>
  <reference>
    <citation>Kappetein AP, Head SJ, Genereux P, Piazza N, van Mieghem NM, Blackstone EH, Brott TG, Cohen DJ, Cutlip DE, van Es GA, Hahn RT, Kirtane AJ, Krucoff MW, Kodali S, Mack MJ, Mehran R, Rodes-Cabau J, Vranckx P, Webb JG, Windecker S, Serruys PW, Leon MB; Valve Academic Research Consortium-2. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. EuroIntervention. 2012 Nov 22;8(7):782-95. doi: 10.4244/EIJV8I7A121.</citation>
    <PMID>23022744</PMID>
  </reference>
  <reference>
    <citation>Leon MB, Piazza N, Nikolsky E, Blackstone EH, Cutlip DE, Kappetein AP, Krucoff MW, Mack M, Mehran R, Miller C, Morel MA, Petersen J, Popma JJ, Takkenberg JJ, Vahanian A, van Es GA, Vranckx P, Webb JG, Windecker S, Serruys PW. Standardized endpoint definitions for Transcatheter Aortic Valve Implantation clinical trials: a consensus report from the Valve Academic Research Consortium. J Am Coll Cardiol. 2011 Jan 18;57(3):253-69. doi: 10.1016/j.jacc.2010.12.005. Epub 2011 Jan 7.</citation>
    <PMID>21216553</PMID>
  </reference>
  <results_reference>
    <citation>Treede H, Lubos E, Conradi L, Deuschl F, Asch FM, Weissman NJ, Schofer N, Schirmer J, Koschyk D, Blankenberg S, Reichenspurner H, Schaefer U. Thirty-day VARC-2 and performance data of a new self-expanding transcatheter aortic heart valve. EuroIntervention. 2015 Nov;11(7):785-92. doi: 10.4244/EIJY15M05_05.</citation>
    <PMID>25983028</PMID>
  </results_reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>September 23, 2014</study_first_submitted>
  <study_first_submitted_qc>September 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>January 21, 2019</last_update_submitted>
  <last_update_submitted_qc>January 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2019</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 Stenosis</mesh_term>
    <mesh_term>Heart Valve Diseases</mesh_term>
    <mesh_term>Constriction, Pathologic</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/NCT02249000
org study id: C1205
nct id: NCT02249000
lead sponsor: 
collaborator: 
has dmc: Yes
First-in-Human clinical investigation to evaluate the safety and clinical performance of the
      BIOVALVE prosthesis in subjects presenting with severe symptomatic aortic valve stenosis,
      which are as judged by the heart team, indicated for transfemoral transcatheter aortic valve
      implantation
In a non-randomized, prospective, multi-center clinical investigation, approximately 86
      eligible subjects will be enrolled.

      Phase 1: BIOVALVE-I feasibility clinical investigation: Approximately 13 eligible subjects
      will be enrolled.

      Phase 2: BIOVALVE-II pilot clinical investigation: Approximately 73 eligible subjects will be
      enrolled.

      BIOVALVE-I/II subjects follow the same clinical investigation plan (CIP) in all aspects.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Early safety at 30 days (Acc. to VARC-2)
time frame: 30 days
description: A composite of all-cause mortality, all stroke (disabling/non-disabling), life-threatening bleeding, acute kidney injury stage 2 or 3 (including renal replacement therapy), coronary artery obstruction requiring intervention, major vascular complication and valve-related dysfunction requiring repeat procedure (balloon aortic valvuloplasty (BAV), transcatheter aortic valve implantation (TAVI), or surgical aortic valve replacement (SAVR)).
measure: Combined safety endpoint at 30 days (Acc. to VARC-1)
time frame: 30 days
description: A composite of all-cause mortality, major stroke, life-threatening (or disabling) bleeding, acute kidney injury stage 3 (including renal replacement therapy), peri-procedural myocardial infarction, major vascular complication and repeat procedure for valve-related dysfunction (surgical or interventional therapy)
measure: Clinical efficacy after 30 days (Acc. to VARC-2):
time frame: 30 days
description: A composite of all-cause mortality, all stroke (disabling and non-disabling), requiring hospitalizations for valve-related symptoms or worsening congestive heart failure, NYHA class III or IV, valve-related dysfunction (mean aortic valve gradient ≥20 mm Hg, effective orifice area (EOA) ≤0.9-1.1 cm2 * and/or Doppler velocity index (DVI) <0.35 m/s, and/or moderate or severe prosthetic valve regurgitation **).
* depending on body surface area
** refers to VARC-2 definitions
measure: Echocardiograhic (ECHO) parameters
time frame: Discharge, 30 days, 6 months, 12 months and annually through 5 years
description: Effective orifice area (EOA) and effective orifice area index (EOAI) Mean prosthetic valve gradient Prosthetic valve regurgitation (Acc. to VARC-1 and VARC-2)
arm group label: BIOVALVE prosthesis
arm group type: Experimental
description: Transcatheter Aortic Valve Replacement (TAVR)
intervention type: Device
intervention name: BIOVALVE prosthesis
description: Transcatheter Aortic Valve Replacement (TAVR)
arm group label: BIOVALVE prosthesis
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Hendrik Treede, MD
role: Study Chair
affiliation: Universitätsklinikum Halle (Saale), Germany
last name: Ulrich Schaefer, MD
role: Study Chair
affiliation: University Heart Center Hamburg, Germany
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: Germany
country: Netherlands
country: Switzerland
citation: Kappetein AP, Head SJ, Genereux P, Piazza N, van Mieghem NM, Blackstone EH, Brott TG, Cohen DJ, Cutlip DE, van Es GA, Hahn RT, Kirtane AJ, Krucoff MW, Kodali S, Mack MJ, Mehran R, Rodes-Cabau J, Vranckx P, Webb JG, Windecker S, Serruys PW, Leon MB; Valve Academic Research Consortium-2. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. EuroIntervention. 2012 Nov 22;8(7):782-95. doi: 10.4244/EIJV8I7A121.
PMID: 23022744
citation: Leon MB, Piazza N, Nikolsky E, Blackstone EH, Cutlip DE, Kappetein AP, Krucoff MW, Mack M, Mehran R, Miller C, Morel MA, Petersen J, Popma JJ, Takkenberg JJ, Vahanian A, van Es GA, Vranckx P, Webb JG, Windecker S, Serruys PW. Standardized endpoint definitions for Transcatheter Aortic Valve Implantation clinical trials: a consensus report from the Valve Academic Research Consortium. J Am Coll Cardiol. 2011 Jan 18;57(3):253-69. doi: 10.1016/j.jacc.2010.12.005. Epub 2011 Jan 7.
PMID: 21216553
citation: Treede H, Lubos E, Conradi L, Deuschl F, Asch FM, Weissman NJ, Schofer N, Schirmer J, Koschyk D, Blankenberg S, Reichenspurner H, Schaefer U. Thirty-day VARC-2 and performance data of a new self-expanding transcatheter aortic heart valve. EuroIntervention. 2015 Nov;11(7):785-92. doi: 10.4244/EIJY15M05_05.
PMID: 25983028
responsible party type: Sponsor
mesh term: Aortic Valve Stenosis
mesh term: Heart Valve Diseases
mesh term: Constriction, Pathologic
sharing ipd: No