<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/NCT03813524</url>
  </required_header>
  <id_info>
    <org_study_id>CP 18-01</org_study_id>
    <nct_id>NCT03813524</nct_id>
  </id_info>
  <brief_title>Cardiovalve Transfemoral Mitral Valve System</brief_title>
  <acronym>AHEAD</acronym>
  <official_title>Early Feasibility Study of the Cardiovalve Transfemoral Mitral Valve System</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston Biomedical Associates</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cardiovalve Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cardiovascular Research Foundation, New York</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Boston Biomedical Associates</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>
      This study is to evaluate the safety and technical performance of the Cardiovalve&#xD;
      Transfemoral Mitral Valve System with its associated procedure, to minimize mitral&#xD;
      regurgitation. Data collected in this clinical study will include 30-day safety and&#xD;
      performance of the device and delivery system, and long-term clinical outcomes over a&#xD;
      follow-up of 5 years.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The Cardiovalve offers a replacement valve delivered through a transfemoral access and&#xD;
      transseptal approach, and is intended to reduce mortality and adverse event rates in selected&#xD;
      patients for whom surgical options are not feasible.&#xD;
&#xD;
      Innovation: A truly transfemoral, trans venous delivery of the valve which minimizes&#xD;
      procedural risk. The Cardiovalve implant has a very low left ventricle (LV) protrusion&#xD;
      footprint thus reducing the risk of LV outflow tract obstruction and/or interference with the&#xD;
      LV. The experience to date is limited but thus far none of the clinical programs has been&#xD;
      halted for safety reasons. Most of the technologies have focused on a transapical delivery&#xD;
      approach (with mini-thoracotomy access) to further simplify the delivery method, with only a&#xD;
      few allowing trans-septal delivery with femoral venous access.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 26, 2019</start_date>
  <completion_date type="Anticipated">December 2028</completion_date>
  <primary_completion_date type="Anticipated">June 2028</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>Cardiovalve Technical Success</measure>
    <time_frame>30 Days</time_frame>
    <description>Successful access, delivery and retrieval of the delivery system; and&#xD;
Successful deployment and correct positioning of the first intended implant; and&#xD;
Freedom from emergency surgery or reintervention related to the device or access procedure&#xD;
Without any procedural mortality, stroke, and device dysfunction (Central MR grade &gt; 1 or paravalvular leak moderate or severe, mean mitral gradient &gt; 6 mm Hg, LVOT obstruction (gradient increase ≥10 mm Hg)) at 30-day follow up.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cardiovalve to be implanted without Major Device Related Adverse Events through 30 Days including:</measure>
    <time_frame>30 Days</time_frame>
    <description>Death (Cardiovascular mortality vs non-cardiovascular);&#xD;
Reintervention (operative or transcatheter) due to progressive or recurrent MR or device related complications;&#xD;
Disabling Stroke;&#xD;
Myocardial infarction (MVARC definition);&#xD;
Major access site and vascular complications&#xD;
Fatal or Life-threatening bleeding (MVARC Type III- V)&#xD;
Life-threatening arrhythmia;&#xD;
Renal Failure requiring dialysis;</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mitral Regurgitation severity</measure>
    <time_frame>30 days, 3 months, 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in LV end diastolic volume index (LVEDVI)</measure>
    <time_frame>30 days, 3 months, 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in LV end systolic volume index (LVESVI)</measure>
    <time_frame>30 days, 3 months, 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in New York Heart Association (NYHA) functional class</measure>
    <time_frame>30 days, 3 months, 6 months</time_frame>
    <description>Class I-IV; Higher functional class represents more severe symptoms of heart failure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6-minute walk test (6MWT) distance</measure>
    <time_frame>30 days, 3 months, 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kansas City Cardiomyopathy Questionnaire (KCCQ) score</measure>
    <time_frame>30 days, 3 months, 6 months</time_frame>
    <description>3 subscales: Symptom Burden- range 0-100; Physical Limitation- range 0-100; Quality of Life- range 0-100;&#xD;
Higher score represents less burdensome symptoms within each subscale. The total KCCQ score represents the mean (average) of the three subscale scores.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Frailty Score</measure>
    <time_frame>30 days, 3 months, 6 months</time_frame>
    <description>Scale from 1 to 9 Lower score indicates a lower level of frailty</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Mitral Regurgitation</condition>
  <arm_group>
    <arm_group_label>Cardiovalve Transfemoral Mitral Valve</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Replacement valve delivered through a transfemoral access and transseptal approach</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Cardiovalve Transfemoral Mitral Valve</intervention_name>
    <description>The Cardiovalve Transfemoral Mitral Valve System is intended for use symptomatic patients with severe mitral regurgitation who are at elevated risk for surgical mitral valve repair or replacement and who are anatomically eligible for transfemoral mitral valve replacement with transseptal access to the left atrium.</description>
    <arm_group_label>Cardiovalve Transfemoral Mitral Valve</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  85&gt;Age ≥ 18 years&#xD;
&#xD;
          -  Symptomatic (Stage D) severe MR confirmed by the echo core lab&#xD;
&#xD;
          -  Cardiac Index &gt; 2.0&#xD;
&#xD;
          -  Left Ventricular Ejection Fraction (LVEF) is ≥ 30% (within 90 days prior to subject&#xD;
             enrollment based upon TTE)&#xD;
&#xD;
          -  New York Heart Association (NYHA) Functional Class II, III or ambulatory IVa&#xD;
&#xD;
          -  Prior treatment with Guideline Directed Medical Therapy (GDMT) for heart failure for&#xD;
             at least 30 days prior to index procedure&#xD;
&#xD;
          -  Patient deemed a high surgical risk per MVARC definition by the site's Heart Team (as&#xD;
             a minimum, one MV cardiac surgeon and one interventional cardiologist, and a cardiac&#xD;
             imaging expert).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  MR etiology that is exclusively Primary (degenerative)&#xD;
&#xD;
          -  Echocardiographic or angiographic evidence of severe mitral annular calcification&#xD;
&#xD;
          -  Echocardiographic evidence of EROA &lt; 0.3cm2&#xD;
&#xD;
          -  Untreated clinically significant coronary artery disease requiring revascularization.&#xD;
&#xD;
          -  Hypertrophic/restrictive cardiomyopathy, constrictive pericarditis, or other&#xD;
             structural heart disease causing heart failure other than other than cardiomyopathy of&#xD;
             either ischemic or non-ischemic etiology&#xD;
&#xD;
          -  Hypotension (systolic pressure &lt; 90 mm Hg)/Cardiogenic shock or other hemodynamic&#xD;
             instability requiring the need for inotropic&#xD;
&#xD;
          -  Fixed pulmonary artery systolic pressure &gt; 2/3 of systemic systolic blood pressure&#xD;
&#xD;
          -  LVEDD &gt;75 mm&#xD;
&#xD;
          -  Severe tricuspid regurgitation or evidence of severe right ventricular dysfunction.&#xD;
&#xD;
          -  Anatomy deemed not suitable for the Cardiovalve&#xD;
&#xD;
          -  Elevated Creatine Kinase-MB (CK-MB)&#xD;
&#xD;
          -  UNOS Status 1 heart transplant or prior orthotropic heart transplantation.&#xD;
&#xD;
          -  Life Expectancy &lt; 1 year due to non-cardiac conditions&#xD;
&#xD;
          -  NYHA functional class IVb&#xD;
&#xD;
          -  Chronic Kidney Disease with Creatinine clearance &lt;30 ml/min/1.73m2&#xD;
&#xD;
          -  Any prior mitral valve surgery or transcatheter mitral valve procedure&#xD;
&#xD;
          -  Stroke or transient ischemic event within 30 Days prior to index procedure&#xD;
&#xD;
          -  Modified Rankin Scale &gt; 4 disability&#xD;
&#xD;
          -  Class I indication for biventricular pacing (in patient with CRT device not implanted)&#xD;
&#xD;
          -  Implant or revision of any rhythm management device (CRT or CRT-D) or implantable&#xD;
             cardioverter-defibrillator within one month prior to index procedure&#xD;
&#xD;
          -  Need for cardiovascular surgery (other than MV disease)&#xD;
&#xD;
          -  Echocardiographic evidence of intracardiac mass, thrombus, or vegetation&#xD;
&#xD;
          -  Active endocarditis&#xD;
&#xD;
          -  Known severe symptomatic carotid stenosis (&gt; 70 % via ultrasound)&#xD;
&#xD;
          -  Active infections requiring current antibiotic therapy&#xD;
&#xD;
          -  Active cancer with expected survival &lt; one year&#xD;
&#xD;
          -  Pregnant or planning pregnancy within next 12 months.&#xD;
&#xD;
          -  Currently participating in an investigational drug or another device study&#xD;
&#xD;
          -  Any condition making it unlikely the patient will be able to complete all procedures&#xD;
&#xD;
          -  Patient (or legal guardian) unable or unwilling to provide written, informed consent&#xD;
             before study enrollment&#xD;
&#xD;
          -  Subjects in whom transesophageal echocardiography is contraindicated&#xD;
&#xD;
          -  Known hypersensitivity or contraindication to procedural, post procedural medication&#xD;
             (e.g., contrast solution, heparin, anticoagulation therapy) or hypersensitivity to&#xD;
             nickel or titanium.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>84 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Piedmont Heart Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center/NYPH</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>February 9, 2023</last_update_submitted>
  <last_update_submitted_qc>February 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 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>Mitral 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/NCT03813524
org study id: CP 18-01
nct id: NCT03813524
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
This study is to evaluate the safety and technical performance of the Cardiovalve
      Transfemoral Mitral Valve System with its associated procedure, to minimize mitral
      regurgitation. Data collected in this clinical study will include 30-day safety and
      performance of the device and delivery system, and long-term clinical outcomes over a
      follow-up of 5 years.
The Cardiovalve offers a replacement valve delivered through a transfemoral access and
      transseptal approach, and is intended to reduce mortality and adverse event rates in selected
      patients for whom surgical options are not feasible.

      Innovation: A truly transfemoral, trans venous delivery of the valve which minimizes
      procedural risk. The Cardiovalve implant has a very low left ventricle (LV) protrusion
      footprint thus reducing the risk of LV outflow tract obstruction and/or interference with the
      LV. The experience to date is limited but thus far none of the clinical programs has been
      halted for safety reasons. Most of the technologies have focused on a transapical delivery
      approach (with mini-thoracotomy access) to further simplify the delivery method, with only a
      few allowing trans-septal delivery with femoral venous access.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Cardiovalve Technical Success
time frame: 30 Days
description: Successful access, delivery and retrieval of the delivery system; and
Successful deployment and correct positioning of the first intended implant; and
Freedom from emergency surgery or reintervention related to the device or access procedure
Without any procedural mortality, stroke, and device dysfunction (Central MR grade > 1 or paravalvular leak moderate or severe, mean mitral gradient > 6 mm Hg, LVOT obstruction (gradient increase ≥10 mm Hg)) at 30-day follow up.
measure: Cardiovalve to be implanted without Major Device Related Adverse Events through 30 Days including:
time frame: 30 Days
description: Death (Cardiovascular mortality vs non-cardiovascular);
Reintervention (operative or transcatheter) due to progressive or recurrent MR or device related complications;
Disabling Stroke;
Myocardial infarction (MVARC definition);
Major access site and vascular complications
Fatal or Life-threatening bleeding (MVARC Type III- V)
Life-threatening arrhythmia;
Renal Failure requiring dialysis;
measure: Mitral Regurgitation severity
time frame: 30 days, 3 months, 6 months
measure: Change in LV end diastolic volume index (LVEDVI)
time frame: 30 days, 3 months, 6 months
measure: Change in LV end systolic volume index (LVESVI)
time frame: 30 days, 3 months, 6 months
measure: Changes in New York Heart Association (NYHA) functional class
time frame: 30 days, 3 months, 6 months
description: Class I-IV; Higher functional class represents more severe symptoms of heart failure
measure: 6-minute walk test (6MWT) distance
time frame: 30 days, 3 months, 6 months
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ) score
time frame: 30 days, 3 months, 6 months
description: 3 subscales: Symptom Burden- range 0-100; Physical Limitation- range 0-100; Quality of Life- range 0-100;
Higher score represents less burdensome symptoms within each subscale. The total KCCQ score represents the mean (average) of the three subscale scores.
measure: Clinical Frailty Score
time frame: 30 days, 3 months, 6 months
description: Scale from 1 to 9 Lower score indicates a lower level of frailty
arm group label: Cardiovalve Transfemoral Mitral Valve
arm group type: Experimental
description: Replacement valve delivered through a transfemoral access and transseptal approach
intervention type: Device
intervention name: Cardiovalve Transfemoral Mitral Valve
description: The Cardiovalve Transfemoral Mitral Valve System is intended for use symptomatic patients with severe mitral regurgitation who are at elevated risk for surgical mitral valve repair or replacement and who are anatomically eligible for transfemoral mitral valve replacement with transseptal access to the left atrium.
arm group label: Cardiovalve Transfemoral Mitral Valve
criteria: 
gender: All
minimum age: 18 Years
maximum age: 84 Years
healthy volunteers: No
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Mitral Valve Insufficiency
sharing ipd: No