<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/NCT03838445</url>
  </required_header>
  <id_info>
    <org_study_id>CL7012</org_study_id>
    <nct_id>NCT03838445</nct_id>
  </id_info>
  <brief_title>Reducing Right Ventricular Failure in Pulmonary Arterial Hypertension (RELIEVE-PAH)</brief_title>
  <acronym>RELIEVE-PAH</acronym>
  <official_title>RELIEVE-PAH TRIAL: REducing Right ventricuLar faIlure With thE V-waVe Shunt in Pulmonary Arterial Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>V-Wave Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>V-Wave Ltd</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>
      The objectives of the RELIEVE-PAH study are to obtain first-in-human experience with the&#xD;
      study device in patients with severe pulmonary arterial hypertension, including evidence of&#xD;
      initial safety, device performance and possible signals of clinical effectiveness.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multi-national, multi-center, prospective, non-randomized, open label trial of&#xD;
      patients implanted with the study device. A total of up to 20 patients will be implanted with&#xD;
      the study device and followed at regular intervals for 1 year and then annually for a total&#xD;
      of 5 years post implant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 14, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2026</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</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>Safety-Percentage of Treatment patients experiencing major device-related adverse events</measure>
    <time_frame>3 months</time_frame>
    <description>Percentage of Treatment group patients experiencing any device-related Major Adverse Cardiovascular or Neurological Events (MACNE) during the first 90-days after implantation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety-Percentage of Treatment patients experiencing any major adverse event</measure>
    <time_frame>3 months</time_frame>
    <description>Percentage of Treatment group patients experiencing any Major Adverse Cardiovascular or Neurological Events (MACNE) during the first 90-days after implantation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Procedure Success-Percentage of patients successfully implanted with study device</measure>
    <time_frame>3 months</time_frame>
    <description>Percentage of patients successfully implanted with the study device at the intended location across the interatrial septum during the index procedure compared to patients with attempted implantations</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Device Success-Percentage of patients implanted with right to left interatrial flow</measure>
    <time_frame>3 months</time_frame>
    <description>Percentage of patients successfully implanted with the study device with right to left interatrial flow on echocardiography at 3 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Freedom from device related MACNE at 1 and 12 months after implantation</measure>
    <time_frame>1 and 12 months</time_frame>
    <description>Freedom from device related Major Adverse Cardiac and Neurologic Events at 1 and 12 months after implantation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in Exercise Capacity between baseline and 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Improvement in Exercise Capacity measured by the six minute hall walk test from baseline to 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in WHO Functional Class between baseline and 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Improvement in World Health Organization Functional Class between baseline and 12 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in Quality of Life between baseline and 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Improvement in Quality of Life as measured by the SF-36 questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in Quality of Life between baseline and 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Improvement in Quality of Life as measured by the CAMPHOR questionnaire</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Pulmonary Arterial Hypertension</condition>
  <arm_group>
    <arm_group_label>Therapy: V-Wave Shunt</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment arm patients will undergo a diagnostic right heart catheterization and invasive echocardiography to determine study eligibility followed by transseptal catheterization and V-Wave Shunt implantation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>V-Wave Interatrial Shunt</intervention_name>
    <description>The V-Wave Interatrial Shunt System, includes a permanent implant placed during a minimally invasive cardiac catheterization procedure using its dedicated Delivery Catheter. The device is implanted through the fossa ovals and straddles the interatrial septum.</description>
    <arm_group_label>Therapy: V-Wave Shunt</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main Inclusion Criteria:&#xD;
&#xD;
          1. Group 1 PAH (idiopathic, connective tissue disease, HIV, corrected congenital heart&#xD;
             disease).&#xD;
&#xD;
          2. WHO Functional Class III or IV symptoms. If WHO Class III, at least 1 High-Risk&#xD;
             characteristic or 2 Intermediate-Risk characteristics from the 2015 ESC Guidelines.&#xD;
&#xD;
          3. Receiving maximal available and tolerable pharmacological PAH therapy ≥3 months at a&#xD;
             stable dose for ≥1 month.&#xD;
&#xD;
        Main Exclusion Criteria:&#xD;
&#xD;
          1. Resting oxygen saturation &lt;90 % without supplemental oxygen corrected for altitude.&#xD;
&#xD;
          2. Mean Right Atrial Pressure &gt;20 mmHg.&#xD;
&#xD;
          3. Severe restrictive or obstructive lung disease.&#xD;
&#xD;
          4. Evidence of organ dysfunction other than right heart failure.&#xD;
&#xD;
          5. Left ventricular ejection fraction &lt;40 %.&#xD;
&#xD;
          6. Anatomical anomaly on transesophageal echocardiography or intracardiac&#xD;
             echocardiography that precludes implantation of Shunt across fossa ovalis (FO) of the&#xD;
             interatrial septum.&#xD;
&#xD;
          7. Inadequate vascular access for implantation of shunt, e.g. femoral venous access for&#xD;
             transseptal catheterization and inferior vena cava (IVC) is not patent.&#xD;
&#xD;
          8. Hemodynamic heart rhythm, or respiratory instability at time of Final Exclusion&#xD;
             Criteria.&#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>Victor Tapson, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cedars-Sinai Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>William T. Abraham, M.D.</last_name>
    <phone>(818)629-2164</phone>
    <email>bill@vwavemedical.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Beverly Walker, MSN, NP</last_name>
    <phone>(818)629-2164</phone>
    <email>beverly@vwavemedical.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Keck Medical Center of USC</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sivagini Ganesh, MD</last_name>
    </contact>
    <investigator>
      <last_name>Sivagini Ganesh, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marc Simon, MD</last_name>
    </contact>
    <investigator>
      <last_name>Marc Simon, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Wexner Medical Center - Davis Heart &amp; Lung Research Institute</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Veronica Franco, MD</last_name>
    </contact>
    <investigator>
      <last_name>Veronica Franco, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval</name>
      <address>
        <city>Québec</city>
        <country>Canada</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Instituto Nacional de Cardiologia</name>
      <address>
        <city>Mexico City</city>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Mexico</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>February 6, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>August 27, 2023</last_update_submitted>
  <last_update_submitted_qc>August 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pulmonary Arterial Hypertension</keyword>
  <keyword>PAH</keyword>
  <keyword>Interatrial Shunt</keyword>
  <keyword>Interatrial Shunting</keyword>
  <keyword>Atrial Septostomy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Arterial Hypertension</mesh_term>
    <mesh_term>Familial Primary Pulmonary Hypertension</mesh_term>
    <mesh_term>Hypertension</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/NCT03838445
org study id: CL7012
nct id: NCT03838445
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
The objectives of the RELIEVE-PAH study are to obtain first-in-human experience with the
      study device in patients with severe pulmonary arterial hypertension, including evidence of
      initial safety, device performance and possible signals of clinical effectiveness.
This is a multi-national, multi-center, prospective, non-randomized, open label trial of
      patients implanted with the study device. A total of up to 20 patients will be implanted with
      the study device and followed at regular intervals for 1 year and then annually for a total
      of 5 years post implant.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety-Percentage of Treatment patients experiencing major device-related adverse events
time frame: 3 months
description: Percentage of Treatment group patients experiencing any device-related Major Adverse Cardiovascular or Neurological Events (MACNE) during the first 90-days after implantation
measure: Safety-Percentage of Treatment patients experiencing any major adverse event
time frame: 3 months
description: Percentage of Treatment group patients experiencing any Major Adverse Cardiovascular or Neurological Events (MACNE) during the first 90-days after implantation
measure: Procedure Success-Percentage of patients successfully implanted with study device
time frame: 3 months
description: Percentage of patients successfully implanted with the study device at the intended location across the interatrial septum during the index procedure compared to patients with attempted implantations
measure: Device Success-Percentage of patients implanted with right to left interatrial flow
time frame: 3 months
description: Percentage of patients successfully implanted with the study device with right to left interatrial flow on echocardiography at 3 months
measure: Freedom from device related MACNE at 1 and 12 months after implantation
time frame: 1 and 12 months
description: Freedom from device related Major Adverse Cardiac and Neurologic Events at 1 and 12 months after implantation.
measure: Improvement in Exercise Capacity between baseline and 12 months
time frame: 12 months
description: Improvement in Exercise Capacity measured by the six minute hall walk test from baseline to 12 months
measure: Improvement in WHO Functional Class between baseline and 12 months
time frame: 12 months
description: Improvement in World Health Organization Functional Class between baseline and 12 months.
measure: Improvement in Quality of Life between baseline and 12 months
time frame: 12 months
description: Improvement in Quality of Life as measured by the SF-36 questionnaire
measure: Improvement in Quality of Life between baseline and 12 months
time frame: 12 months
description: Improvement in Quality of Life as measured by the CAMPHOR questionnaire
arm group label: Therapy: V-Wave Shunt
arm group type: Experimental
description: Treatment arm patients will undergo a diagnostic right heart catheterization and invasive echocardiography to determine study eligibility followed by transseptal catheterization and V-Wave Shunt implantation.
intervention type: Device
intervention name: V-Wave Interatrial Shunt
description: The V-Wave Interatrial Shunt System, includes a permanent implant placed during a minimally invasive cardiac catheterization procedure using its dedicated Delivery Catheter. The device is implanted through the fossa ovals and straddles the interatrial septum.
arm group label: Therapy: V-Wave Shunt
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Victor Tapson, M.D.
role: Principal Investigator
affiliation: Cedars-Sinai Medical Center
last name: William T. Abraham, M.D.
phone: (818)629-2164
email: bill@vwavemedical.com
last name: Beverly Walker, MSN, NP
phone: (818)629-2164
email: beverly@vwavemedical.com
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Withdrawn
facility: 
status: Active, not recruiting
country: Canada
country: Mexico
country: United States
responsible party type: Sponsor
mesh term: Pulmonary Arterial Hypertension
mesh term: Familial Primary Pulmonary Hypertension
mesh term: Hypertension