<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/NCT03779620</url>
  </required_header>
  <id_info>
    <org_study_id>CW19-01</org_study_id>
    <nct_id>NCT03779620</nct_id>
  </id_info>
  <brief_title>Valvosoft First-In-Man Study in Severe Symptomatic Aortic Stenosis</brief_title>
  <official_title>Prospective, Controlled, Single-arm Clinical Investigation for the Treatment of Subjects With Severe Symptomatic Aortic Valve Stenosis Using Valvosoft® Pulsed Cavitational Ultrasound Therapy (PCUT) - First-In-Man</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cardiawave SA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cardiawave SA</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>
      This is a prospective, controlled, single-arm clinical investigation for the treatment of&#xD;
      subjects with severe symptomatic aortic valve stenosis using Valvosoft® Pulsed Cavitational&#xD;
      Ultrasound Therapy (PCUT) - First-In-man&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      CARDIAWAVE has developed a new non-invasive, real-time image-guided, therapeutic approach to&#xD;
      treat patients suffering from Calcified Aortic Stenosis. CARDIAWAVE's Valvosoft device is a&#xD;
      new ultrasound therapy based on a disruptive technology involving delivering an extremely&#xD;
      precise and focused ultrasound beam to perform a reparative effect on the aortic valve&#xD;
      leaflets, softening the valve's tissues, restoring leaflet mobility, and therefore improving&#xD;
      the overall clinical status related to the aortic valve stenosis. This is a FIM study&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 13, 2019</start_date>
  <completion_date type="Anticipated">December 1, 2023</completion_date>
  <primary_completion_date type="Actual">January 15, 2022</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>
    <intervention_model_description>Ultrasound treatment of calcified aortic valve stenosis</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety: Rate of procedure related mortality at 30 days</measure>
    <time_frame>30 days post-procedure</time_frame>
    <description>Rate of procedure related mortality at 30 days</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Device performance to modify valve structure as measured by echocardiography</measure>
    <time_frame>Immediately post-procedure</time_frame>
    <description>Ability to modify the Aortic Valve Area (mm2)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Device performance to modify valve structure as measured by echocardiography</measure>
    <time_frame>Immediately post-procedure</time_frame>
    <description>Ability to modify the Pressure Gradient (mmHg)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality and major adverse events (MAE's)</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Rate of all-cause mortality and MAE's peri and postprocedure and at 1, 3, 6, 12 and 24 months post operatively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-disabling stroke</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Rate of stroke at 1,3,6, 12 and 24 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement of clinical status</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Improvement of New York Heart Association class (I-IV - stage of severity of heart failure - I=no symptoms, IV= symptoms at rest) at 1,3,6,12, and 24 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of all Adverse Events (AEs)</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Rate of AE's reported at at 1, 3, 6, 12 and 24 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>User handeling of Valvosoft</measure>
    <time_frame>Immediately post-procedure</time_frame>
    <description>User handling (questionnaire for operator + procedure duration) immediately post-procedure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement of quality of life</measure>
    <time_frame>upto 24 months</time_frame>
    <description>Improvement of quality of life by means of Kansas City Cardiomyopathy Questionnaire at 1, 3, 6, 12 and 24 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long term maintenance of improvement of AVA and PG</measure>
    <time_frame>upto 24 months</time_frame>
    <description>Long term maintenance of improvement of AVA and PG at 3, 6, 12 and 24 months</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Aortic Valve Stenosis</condition>
  <arm_group>
    <arm_group_label>Ultrasound treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ultrasound treatment of patients with symptomatic aortic valve stenosis who are not eligible for valve replacement</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Ultrasound treatment of Calcified aortic valve</intervention_name>
    <description>Ultrasound treatment of calcified aortic valve causing symptomatic aortic valve stenosis in patients who are not eligible for valve replacement</description>
    <arm_group_label>Ultrasound treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects suffering from severe symptomatic aortic valve stenosis (including subjects&#xD;
             with a bicuspid valve).&#xD;
&#xD;
          2. Patient is not eligible for TAVR/SAVR .&#xD;
&#xD;
          3. Age ≥18 years.&#xD;
&#xD;
          4. Subjects who are willing to provide a written informed consent prior to participating&#xD;
             in the study.&#xD;
&#xD;
          5. Subjects who can comply with the study follow up or other study requirements.&#xD;
&#xD;
          6. Subject eligible according to Clinical Review Committee&#xD;
&#xD;
             -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with any electrical device implanted.&#xD;
&#xD;
          2. Subjects with unstable arrhythmia not controlled by medical treatment.&#xD;
&#xD;
          3. Subjects with implanted mechanical valve in any position or bio prosthetic valve in&#xD;
             aortic position.&#xD;
&#xD;
          4. Subjects with complex congenital heart disease.&#xD;
&#xD;
          5. Chest deformity.&#xD;
&#xD;
          6. Cardiogenic shock.&#xD;
&#xD;
          7. History of heart transplant.&#xD;
&#xD;
          8. Subjects requiring other cardiac surgery procedures (bypass graft surgery, mitral&#xD;
             valve procedure, tricuspid valve procedure) within one month after treatment.&#xD;
&#xD;
          9. Thrombus in heart.&#xD;
&#xD;
         10. Acute myocardial infarction (MI), stroke or transient ischemic attack (TIA) within one&#xD;
             month prior to enrolment*.&#xD;
&#xD;
         11. Subjects who are pregnant or nursing.&#xD;
&#xD;
         12. Subjects who are participating in another research study for which the primary&#xD;
             endpoint has not been reached.&#xD;
&#xD;
             -&#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>Emmanuel Messas, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>HGEP Paris, France</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Européen Georges Pompidou</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amphia Hospital</name>
      <address>
        <city>Breda</city>
        <zip>4818CK</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>November 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 17, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>March 27, 2023</last_update_submitted>
  <last_update_submitted_qc>March 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>symptomatic</keyword>
  <keyword>aortic valve</keyword>
  <keyword>stenosis</keyword>
  <keyword>ultrasound</keyword>
  <keyword>non-invasive</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aortic Valve Stenosis</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/NCT03779620
org study id: CW19-01
nct id: NCT03779620
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a prospective, controlled, single-arm clinical investigation for the treatment of
      subjects with severe symptomatic aortic valve stenosis using Valvosoft® Pulsed Cavitational
      Ultrasound Therapy (PCUT) - First-In-man
CARDIAWAVE has developed a new non-invasive, real-time image-guided, therapeutic approach to
      treat patients suffering from Calcified Aortic Stenosis. CARDIAWAVE's Valvosoft device is a
      new ultrasound therapy based on a disruptive technology involving delivering an extremely
      precise and focused ultrasound beam to perform a reparative effect on the aortic valve
      leaflets, softening the valve's tissues, restoring leaflet mobility, and therefore improving
      the overall clinical status related to the aortic valve stenosis. This is a FIM study
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Ultrasound treatment of calcified aortic valve stenosis
primary purpose: Treatment
masking: None (Open Label)
measure: Safety: Rate of procedure related mortality at 30 days
time frame: 30 days post-procedure
description: Rate of procedure related mortality at 30 days
measure: Device performance to modify valve structure as measured by echocardiography
time frame: Immediately post-procedure
description: Ability to modify the Aortic Valve Area (mm2)
measure: Device performance to modify valve structure as measured by echocardiography
time frame: Immediately post-procedure
description: Ability to modify the Pressure Gradient (mmHg)
measure: All-cause mortality and major adverse events (MAE's)
time frame: Up to 24 months
description: Rate of all-cause mortality and MAE's peri and postprocedure and at 1, 3, 6, 12 and 24 months post operatively.
measure: Non-disabling stroke
time frame: Up to 24 months
description: Rate of stroke at 1,3,6, 12 and 24 months
measure: Improvement of clinical status
time frame: Up to 24 months
description: Improvement of New York Heart Association class (I-IV - stage of severity of heart failure - I=no symptoms, IV= symptoms at rest) at 1,3,6,12, and 24 months.
measure: Number of all Adverse Events (AEs)
time frame: Up to 24 months
description: Rate of AE's reported at at 1, 3, 6, 12 and 24 months
measure: User handeling of Valvosoft
time frame: Immediately post-procedure
description: User handling (questionnaire for operator + procedure duration) immediately post-procedure
measure: Improvement of quality of life
time frame: upto 24 months
description: Improvement of quality of life by means of Kansas City Cardiomyopathy Questionnaire at 1, 3, 6, 12 and 24 months
measure: Long term maintenance of improvement of AVA and PG
time frame: upto 24 months
description: Long term maintenance of improvement of AVA and PG at 3, 6, 12 and 24 months
arm group label: Ultrasound treatment
arm group type: Experimental
description: Ultrasound treatment of patients with symptomatic aortic valve stenosis who are not eligible for valve replacement
intervention type: Device
intervention name: Ultrasound treatment of Calcified aortic valve
description: Ultrasound treatment of calcified aortic valve causing symptomatic aortic valve stenosis in patients who are not eligible for valve replacement
arm group label: Ultrasound treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Emmanuel Messas, MD
role: Principal Investigator
affiliation: HGEP Paris, France
facility: 
facility: 
country: France
country: Netherlands
responsible party type: Sponsor
mesh term: Aortic Valve Stenosis
mesh term: Constriction, Pathologic
sharing ipd: No