Clinical trial NCT04475393: Carmat Total Artificial Heart As a Bridge to Transplant in Patients with Advanced Heart Failure
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Advanced Heart Failure
Lead sponsor: Carmat SA
Sponsor class: INDUSTRY
First posted: 2020-07-17
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

1. Patient 18 years or older
2. Patient in the waiting list for heart transplant or temporarily contraindicated for heart transplant
3. On inotropes or cardiac Index (CI) \< 2.2 L/min/m2
4. On Optimal Medical Management as judged by the investigator based on current Heart Failure practice guidelines (ESC/HAS)
5. Eligible to biventricular Mechanical Circulatory Support according to one of the following category:

   1. Biventricular failure with at least two of the following hemodynamic/ echocardiographic measurements implying right heart failure:

      * RVEF ≤ 30% or FAC \< 35%
      * RVSWI ≤ 0.25 mmHg\*L/m2
      * TAPSE ≤ 14mm
      * RV-to-LV end-diastolic diameter ratio \> 0.72
      * CVP \> 15 mmHg or persistence of echographic and/or biological signs of hepatic congestion
      * CVP-to-PCWP ratio \> 0.63
      * PAP index \<2
      * Tricuspid insufficiency grade 4
   2. Treatment-refractory recurrent and sustained ventricular tachycardia or ventricular fibrillation in the presence of untreatable arrhythmogenic pathologic substrate.
   3. Heart failure due to restrictive or constrictive physiology (e.g., hypertrophic cardiomyopathy, cardiac amyloidosis / senile or other infiltrative heart disease)
6. Anatomic compatibility confirmed using 3D imaging (CT-scan) and by the screening committee (for Cohort 1).
7. Patient's affiliation to health care insurance
8. Patient has signed the informed consent.

Exclusion Criteria:

1. Absolute contra-indication for heart transplant
2. Existence of any ongoing non-temporary mechanical circulatory support
3. Existence of any ongoing peripheral mechanical circulatory support such as ECMO, Impella (all types), IABP with a support duration \> 21 days
4. Patient intubated and unconscious; or intubated and not awake
5. Known intolerance to anticoagulant or antiplatelet therapies or known Heparin Induced Thrombocytopenia.
6. Coagulopathy defined by platelets \< 100G/l or INR ≥ 1.5 not due to anticoagulant therapy.
7. Known thrombophilia (Antithrombin III, protein C or S deficiency) or any recurrent venous thromboembolic events requiring long term curative oral anticoagulation.
8. Cerebrovascular accident \< 3 months or symptomatic (Rankin score \>1; Glasgow score \< 14) or a known \> 80% carotid stenosis.
9. Known abdominal or thoracic aortic aneurysm \> 5 cm that has not been treated.
10. Severe end-organ dysfunction as per the following criteria:

    1. Total bilirubin \> 45 µmol/l (2.65 mg/dl) or cirrhosis evidenced by ultrasound, IRM and positive biopsy
    2. GFR \< 30ml/min/1.73m2 (with no hemodialysis)
11. History of severe Chronic Obstructive Pulmonary Disease or severe restrictive lung disease with FEV1/FVC \<0.7 and FEV1\<50% predicted.
12. Recent active blood stream infection confirmed by a positive hemoculture within 48 hours.
13. Documented amyloid light-chain (AL amyloidosis).
14. Hemodynamically significant peripheral vascular disease assessed by clinical exam.
15. Illness, other than heart disease, that would limit survival to less than 2 years.
16. Irreversible cognitive dysfunction, psycho-cognitive disabilities, psycho-social issues or psychiatric disease, likely to impair compliance with the study protocol and TAH management that in the opinion of the investigator could interfere with the ability to manage the therapy (i.e. non-compliance to heart failure therapy, uncontrolled diabetes, mental health issue, etc.).
17. Pregnancy or breast feeding (woman in childbearing age will have to show negative pregnancy test).
18. Patient is currently enrolled or has participated in the last 30 days in another therapeutic or interventional clinical study that is likely to confound the study results or affect the study.

Primary outcomes:
measure: Survival free of disabling stroke at 180 days post-implant
timeFrame: 180 days
Secondary outcomes:
measure: Overall survival
timeFrame: 180 days - 1 year
measure: General Health Status change
timeFrame: 180 days - 1 and 2 years
measure: Change in functional status measured by the Six Minutes Walk Test
timeFrame: 180 days - 1 and 2 years
measure: Change in functional status
timeFrame: 180 days - 1 and 2 years
measure: Adverse Events
timeFrame: 180 days - 1 and 2 years
measure: Hospital re-admissions rate
timeFrame: 180 days - 1 and 2 years
measure: Healthcare costs
timeFrame: 180 days - 1 and 2 years
measure: Quality Adjusted Life Years
timeFrame: 180 days - 1 and 2 years
Other outcomes:
Locations:
city: Bron
country: France
facility: Hôpital Louis Pradel
city: Dijon
country: France
facility: CHU Dijon
city: Le Plessis-Robinson
country: France
facility: Hôpital Marie Lannelongue
city: Lille
country: France
facility: Centre Hospitalier Régional Universitaire
city: Montpellier
country: France
facility: CHRU Montpellier
city: Nantes
country: France
facility: Hôpital Laennec
city: Paris
country: France
facility: Groupe Hospitalier Pitié-Salpêtrière,
city: Paris
country: France
facility: Hôpital Européen George Pompidou
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Strasbourg
country: France
facility: Nouvel Hôpital Civil
Study officials:
affiliation: Carmat SA
name: Piet Jansen, MD
role: STUDY_DIRECTOR
References: