<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/NCT04475393</url>
  </required_header>
  <id_info>
    <org_study_id>CAR2019-FR</org_study_id>
    <nct_id>NCT04475393</nct_id>
  </id_info>
  <brief_title>Carmat Total Artificial Heart as a Bridge to Transplant in Patients With Advanced Heart Failure</brief_title>
  <acronym>EFICAS</acronym>
  <official_title>Multicentric Prospective Cohort Study in Patients With Irreversible Biventricular Heart Failure to Assess the Efficacy and Safety of Carmat TAH, Its Clinical Utility and Cost, as a Bridge to Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Carmat SA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Carmat 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>
      The objective of this clinical investigation is to evaluate the efficacy and the safety of&#xD;
      the Carmat Total Artificial Heart for the treatment of refractory advanced heart failure in&#xD;
      transplant eligible patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A selection committee (composed of two independent experts in the field of cardiovascular&#xD;
      surgery/cardiology and of PIs) assess the subject eligibility based on clinical and anatomic&#xD;
      criteria. Clinically eligible patients will be distributed into two cohorts depending on&#xD;
      their anatomic compatibility with the device:&#xD;
&#xD;
        -  cohort 1: patients that are anatomically compatible will receive the Carmat TAH ;&#xD;
&#xD;
        -  cohort 2: patients that are not anatomically compatible will receive standard therapy&#xD;
&#xD;
      The efficacy and safety of the Carmat TAH will be assessed in cohort 1 and compared to a&#xD;
      level of efficacy defined by the published data on the commercially available TAH; and&#xD;
      adjusted for INTERMACS patient profile.&#xD;
&#xD;
      The clinical utility and the costs of Carmat TAH will be assessed by comparing the cohort of&#xD;
      subject receiving the Carmat TAH to the cohort of patients treated by standard therapy&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 12, 2022</start_date>
  <completion_date type="Anticipated">April 2027</completion_date>
  <primary_completion_date type="Anticipated">April 2025</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>Survival free of disabling stroke at 180 days post-implant</measure>
    <time_frame>180 days</time_frame>
    <description>Success is defined as survival free of disabling stroke (Modified Rankin score &gt;3) at 180 days after Carmat TAH&#xD;
implantation or transplanted if before 180 days.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>180 days - 1 year</time_frame>
    <description>Survival post-implant; Survival post-transplantation (Kaplan-Meier)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>General Health Status change</measure>
    <time_frame>180 days - 1 and 2 years</time_frame>
    <description>Measured with the EuroQol EQ-5D-5L questionnaire, health-related quality of life consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which can take one of five responses (EQ-5D-5L). The responses record five levels of severity (1:no problems; 2:slight problems; 3:moderate problems 4:severe problems; 5:extreme problems) within a particular EQ-5D dimension.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in functional status measured by the Six Minutes Walk Test</measure>
    <time_frame>180 days - 1 and 2 years</time_frame>
    <description>The 6-min walk test is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6-minute walk distance provides a measure for integrated global response of multiple cardiopulmonary and musculoskeletal systems involved in exercise.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in functional status</measure>
    <time_frame>180 days - 1 and 2 years</time_frame>
    <description>New York Heart Association (NYHA) functional classification (regression scale I, II, III, IV)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>180 days - 1 and 2 years</time_frame>
    <description>Adverse Event Rates will be captured per the INTERMACS definitions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital re-admissions rate</measure>
    <time_frame>180 days - 1 and 2 years</time_frame>
    <description>Rate of unplanned re-admissions to the hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Healthcare costs</measure>
    <time_frame>180 days - 1 and 2 years</time_frame>
    <description>The healthcare resources used to treat the patient during the two-year period, including those related to selection, those related to waiting for transplantation (whatever the therapeutic strategy), to transplantation, post-transplant management and any adverse event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality Adjusted Life Years</measure>
    <time_frame>180 days - 1 and 2 years</time_frame>
    <description>The Quality Adjusted Life Years, evaluated during the two-year period, values the health outcomes in a single measure by combining both quality of life (evaluated by EuroQol EQ-5D-5L) and lenght of life.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">52</enrollment>
  <condition>Advanced Heart Failure</condition>
  <arm_group>
    <arm_group_label>Carmat TAH</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects implanted with Carmat TAH</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Carmat Total Artificial Heart</intervention_name>
    <description>Heart Replacement Therapy</description>
    <arm_group_label>Carmat TAH</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient 18 years or older&#xD;
&#xD;
          2. Patient in the waiting list for heart transplant or temporarily contraindicated for&#xD;
             heart transplant&#xD;
&#xD;
          3. Inotrope dependent* or cardiac Index (CI) &lt; 2.2 L/min/m2 if inotropes are&#xD;
             contra-indicated (heart failure due to restrictive or constrictive physiology).&#xD;
&#xD;
             * Inotrope dependence needs to be confirmed by failed weaning or justified in medical&#xD;
             records.&#xD;
&#xD;
          4. On Optimal Medical Management as judged by the investigator based on current Heart&#xD;
             Failure practice guidelines (ESC/HAS)&#xD;
&#xD;
          5. Eligible to biventricular Mechanical Circulatory Support according to one of the&#xD;
             following category:&#xD;
&#xD;
               1. Biventricular failure with at least two of the following hemodynamic/&#xD;
                  echocardiographic measurements implying right heart failure:&#xD;
&#xD;
                    -  RVEF ≤ 30%&#xD;
&#xD;
                    -  RVSWI ≤ 0.25 mmHg*L/m2&#xD;
&#xD;
                    -  TAPSE ≤ 14mm&#xD;
&#xD;
                    -  RV-to-LV end-diastolic diameter ratio &gt; 0.72&#xD;
&#xD;
                    -  CVP &gt; 15 mmHg&#xD;
&#xD;
                    -  CVP-to-PCWP ratio &gt; 0.63&#xD;
&#xD;
                    -  PAP index &lt;2&#xD;
&#xD;
                    -  Tricuspid insufficiency grade 4&#xD;
&#xD;
               2. Treatment-refractory recurrent and sustained ventricular tachycardia or&#xD;
                  ventricular fibrillation in the presence of untreatable arrhythmogenic pathologic&#xD;
                  substrate.&#xD;
&#xD;
               3. Heart failure due to restrictive or constrictive physiology (e.g., hypertrophic&#xD;
                  cardiomyopathy, cardiac amyloidosis / senile or other infiltrative heart disease)&#xD;
&#xD;
          6. Anatomic compatibility confirmed using 3D imaging (CT-scan) and by the screening&#xD;
             committee (for Cohort 1).&#xD;
&#xD;
          7. Patient's affiliation to health care insurance&#xD;
&#xD;
          8. Patient has signed the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Absolute contra-indication for heart transplant&#xD;
&#xD;
          2. Existence of any ongoing non-temporary mechanical circulatory support&#xD;
&#xD;
          3. Existence of any ongoing peripheral mechanical circulatory support such as ECMO,&#xD;
             Impella (all types), IABP with a support duration &gt; 21 days&#xD;
&#xD;
          4. Patient intubated and unconscious; or intubated and not awake&#xD;
&#xD;
          5. Known intolerance to anticoagulant or antiplatelet therapies or known Heparin Induced&#xD;
             Thrombocytopenia.&#xD;
&#xD;
          6. Coagulopathy defined by platelets &lt; 100G/l or INR ≥ 1.5 not due to anticoagulant&#xD;
             therapy.&#xD;
&#xD;
          7. Known thrombophilia (Antithrombin III, protein C or S deficiency) or any recurrent&#xD;
             venous thromboembolic events requiring long term curative oral anticoagulation.&#xD;
&#xD;
          8. Cerebrovascular accident &lt; 3 months or symptomatic (Rankin score &gt;1; Glasgow score &lt;&#xD;
             14) or a known &gt; 80% carotid stenosis.&#xD;
&#xD;
          9. Known abdominal or thoracic aortic aneurysm &gt; 5 cm that has not been treated.&#xD;
&#xD;
         10. Severe end-organ dysfunction as per the following criteria:&#xD;
&#xD;
               1. Total bilirubin &gt; 45 µmol/l (2.65 mg/dl) or cirrhosis evidenced by ultrasound,&#xD;
                  IRM and positive biopsy&#xD;
&#xD;
               2. GFR &lt; 40ml/min/1.73m2 (with no hemodialysis)&#xD;
&#xD;
         11. History of severe Chronic Obstructive Pulmonary Disease or severe restrictive lung&#xD;
             disease with FEV1/FVC &lt;0.7 and FEV1&lt;50% predicted.&#xD;
&#xD;
         12. Recent active blood stream infection confirmed by a positive hemoculture within 48&#xD;
             hours.&#xD;
&#xD;
         13. Documented amyloid light-chain (AL amyloidosis).&#xD;
&#xD;
         14. Hemodynamically significant peripheral vascular disease assessed by clinical exam.&#xD;
&#xD;
         15. Illness, other than heart disease, that would limit survival to less than 2 years.&#xD;
&#xD;
         16. Irreversible cognitive dysfunction, psycho-cognitive disabilities, psycho-social&#xD;
             issues or psychiatric disease, likely to impair compliance with the study protocol and&#xD;
             TAH management that in the opinion of the investigator could interfere with the&#xD;
             ability to manage the therapy (i.e. non-compliance to heart failure therapy,&#xD;
             uncontrolled diabetes, mental health issue, etc.).&#xD;
&#xD;
         17. Pregnancy or breast feeding (woman in childbearing age will have to show negative&#xD;
             pregnancy test).&#xD;
&#xD;
         18. Patient is currently enrolled or has participated in the last 30 days in another&#xD;
             therapeutic or interventional clinical study that is likely to confound the study&#xD;
             results or affect the study.&#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>Piet Jansen, MD</last_name>
    <role>Study Director</role>
    <affiliation>Carmat SA</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Soumia Aoualli</last_name>
    <phone>+33 63 826 5953</phone>
    <email>clinique@carmatsas.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Elisabeth Vacher</last_name>
    <email>clinique@carmatsas.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hôpital Louis Pradel</name>
      <address>
        <city>Bron</city>
        <zip>69500</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean-François Obadia, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Régional Universitaire</name>
      <address>
        <city>Lille</city>
        <zip>59000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>André Vincentelli, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Groupe Hospitalier Pitié-Salpêtrière,</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pascal Leprince, MD, PhD</last_name>
    </contact>
    <contact_backup>
      <last_name>Guillaume Lebreton, MD, PhD</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Hôpital Européen George Pompidou</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paul Achouh</last_name>
    </contact>
    <contact_backup>
      <last_name>MD</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Hôpital Pontchaillou</name>
      <address>
        <city>Rennes</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Erwan Flecher, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Nouvel Hôpital Civil</name>
      <address>
        <city>Strasbourg</city>
        <zip>67000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michel Kindo, MD, PhD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>January 19, 2023</last_update_submitted>
  <last_update_submitted_qc>January 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 20, 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>Heart Failure</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/NCT04475393
org study id: CAR2019-FR
nct id: NCT04475393
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The objective of this clinical investigation is to evaluate the efficacy and the safety of
      the Carmat Total Artificial Heart for the treatment of refractory advanced heart failure in
      transplant eligible patients.
A selection committee (composed of two independent experts in the field of cardiovascular
      surgery/cardiology and of PIs) assess the subject eligibility based on clinical and anatomic
      criteria. Clinically eligible patients will be distributed into two cohorts depending on
      their anatomic compatibility with the device:

        -  cohort 1: patients that are anatomically compatible will receive the Carmat TAH ;

        -  cohort 2: patients that are not anatomically compatible will receive standard therapy

      The efficacy and safety of the Carmat TAH will be assessed in cohort 1 and compared to a
      level of efficacy defined by the published data on the commercially available TAH; and
      adjusted for INTERMACS patient profile.

      The clinical utility and the costs of Carmat TAH will be assessed by comparing the cohort of
      subject receiving the Carmat TAH to the cohort of patients treated by standard therapy
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Survival free of disabling stroke at 180 days post-implant
time frame: 180 days
description: Success is defined as survival free of disabling stroke (Modified Rankin score >3) at 180 days after Carmat TAH
implantation or transplanted if before 180 days.
measure: Overall survival
time frame: 180 days - 1 year
description: Survival post-implant; Survival post-transplantation (Kaplan-Meier)
measure: General Health Status change
time frame: 180 days - 1 and 2 years
description: Measured with the EuroQol EQ-5D-5L questionnaire, health-related quality of life consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which can take one of five responses (EQ-5D-5L). The responses record five levels of severity (1:no problems; 2:slight problems; 3:moderate problems 4:severe problems; 5:extreme problems) within a particular EQ-5D dimension.
measure: Change in functional status measured by the Six Minutes Walk Test
time frame: 180 days - 1 and 2 years
description: The 6-min walk test is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6-minute walk distance provides a measure for integrated global response of multiple cardiopulmonary and musculoskeletal systems involved in exercise.
measure: Change in functional status
time frame: 180 days - 1 and 2 years
description: New York Heart Association (NYHA) functional classification (regression scale I, II, III, IV)
measure: Adverse Events
time frame: 180 days - 1 and 2 years
description: Adverse Event Rates will be captured per the INTERMACS definitions
measure: Hospital re-admissions rate
time frame: 180 days - 1 and 2 years
description: Rate of unplanned re-admissions to the hospital
measure: Healthcare costs
time frame: 180 days - 1 and 2 years
description: The healthcare resources used to treat the patient during the two-year period, including those related to selection, those related to waiting for transplantation (whatever the therapeutic strategy), to transplantation, post-transplant management and any adverse event
measure: Quality Adjusted Life Years
time frame: 180 days - 1 and 2 years
description: The Quality Adjusted Life Years, evaluated during the two-year period, values the health outcomes in a single measure by combining both quality of life (evaluated by EuroQol EQ-5D-5L) and lenght of life.
arm group label: Carmat TAH
arm group type: Experimental
description: Subjects implanted with Carmat TAH
intervention type: Device
intervention name: Carmat Total Artificial Heart
description: Heart Replacement Therapy
arm group label: Carmat TAH
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Piet Jansen, MD
role: Study Director
affiliation: Carmat SA
last name: Soumia Aoualli
phone: +33 63 826 5953
email: clinique@carmatsas.com
last name: Elisabeth Vacher
email: clinique@carmatsas.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Heart Failure
sharing ipd: No