Carmat Total Artificial Heart As a Bridge to Transplant in Patients with Advanced Heart Failure

Not Applicable

Recruiting

• Conditions: Advanced Heart Failure
• Interventions: Device: Carmat Total Artificial Heart

• Registration Number: NCT04475393
• Lead Sponsor: Carmat SA

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

Study Timeline

• Study First Submitted: 2020-07-14
• Study First Submitted QC: 2020-07-14
• Study First Posted: 2020-07-17
• Study Start: 2022-12-12
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-25
• Last Update Posted: 2025-01-28
• Primary Completion: 2025-04
• Study Completion: 2027-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 52

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Carmat TAH	Carmat Total Artificial Heart	Subjects implanted with Carmat TAH

Primary Outcome Measures

Name	Time	Method
Survival free of disabling stroke at 180 days post-implant	180 days	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.

Secondary Outcome Measures

Name	Time	Method
Change in functional status measured by the Six Minutes Walk Test	180 days - 1 and 2 years	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.
General Health Status change	180 days - 1 and 2 years	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.
Hospital re-admissions rate	180 days - 1 and 2 years	Rate of unplanned re-admissions to the hospital
Overall survival	180 days - 1 year	Survival post-implant; Survival post-transplantation (Kaplan-Meier)
Adverse Events	180 days - 1 and 2 years	Adverse Event Rates will be captured per the INTERMACS definitions
Quality Adjusted Life Years	180 days - 1 and 2 years	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.
Change in functional status	180 days - 1 and 2 years	New York Heart Association (NYHA) functional classification (regression scale I, II, III, IV)
Healthcare costs	180 days - 1 and 2 years	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

Trial Locations

Locations (10)

CHRU Montpellier; 🇫🇷 Montpellier, France

Hôpital Laennec; 🇫🇷 Nantes, France

Hôpital Louis Pradel; 🇫🇷 Bron, France

CHU Dijon; 🇫🇷 Dijon, France

Hôpital Marie Lannelongue; 🇫🇷 Le Plessis-Robinson, France

Hôpital Européen George Pompidou; 🇫🇷 Paris, France

Hôpital Pontchaillou; 🇫🇷 Rennes, France

Nouvel Hôpital Civil; 🇫🇷 Strasbourg, France

Centre Hospitalier Régional Universitaire; 🇫🇷 Lille, France

Groupe Hospitalier Pitié-Salpêtrière,; 🇫🇷 Paris, France