Carmat Total Artificial Heart for patients with advanced heart failure

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

This study is testing whether the Carmat Total Artificial Heart can help people with severe heart failure who are waiting for a transplant feel better compared to standard treatments.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 52 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Carmat SA (Industry-sponsored)
• Locations: 10 sites (Bron and 9 other locations)
• Trial ID: NCT04475393 on ClinicalTrials.gov

What this trial studies

This clinical investigation evaluates the efficacy and safety of the Carmat Total Artificial Heart (TAH) in patients with refractory advanced heart failure who are eligible for heart transplant. Patients will be assessed for eligibility based on clinical and anatomic criteria and divided into two cohorts: those compatible with the Carmat TAH and those receiving standard therapy. The study aims to compare the outcomes of the Carmat TAH with existing treatment options, focusing on clinical utility and cost-effectiveness.

Who should consider this trial

Good fit: Ideal candidates are patients aged 18 and older who are on the waiting list for a heart transplant or temporarily contraindicated for one, and who are experiencing advanced heart failure.

Not a fit: Patients who are not eligible for biventricular Mechanical Circulatory Support or those with conditions not addressed by the Carmat TAH may not benefit from this study.

Why it matters

Potential benefit: If successful, this could provide a new treatment option for patients with advanced heart failure, potentially improving survival rates and quality of life.

How similar studies have performed: Other studies have explored artificial hearts, but the Carmat TAH represents a novel approach in this specific patient population.

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.

Where this trial is running

Bron and 9 other locations

• Hôpital Louis Pradel — Bron, France (Recruiting)
• CHU Dijon — Dijon, France (Recruiting)
• Hôpital Marie Lannelongue — Le Plessis-Robinson, France (Recruiting)
• Centre Hospitalier Régional Universitaire — Lille, France (Recruiting)
• CHRU Montpellier — Montpellier, France (Recruiting)
• Hôpital Laennec — Nantes, France (Recruiting)
• Groupe Hospitalier Pitié-Salpêtrière, — Paris, France (Recruiting)
• Hôpital Européen George Pompidou — Paris, France (Recruiting)
• Hôpital Pontchaillou — Rennes, France (Recruiting)
• Nouvel Hôpital Civil — Strasbourg, France (Recruiting)

Study contacts

• Study coordinator: Soumia Aoualli

Conditions Advanced Heart Failure