Carmat Total Artificial Heart as a Bridge to Transplant in Patients With Advanced Heart Failure (EFICAS)

Multicentric Prospective Cohort Study in Patients With Irreversible Biventricular Heart Failure to Assess the Efficacy and Safety of Carmat TAH, Clinical Utility and Cost, as a Bridge to Transplantation

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Heart Failure
• Intervention / Treatment: Device: Carmat Total Artificial Heart; Other: Standard therapy for heart failure

Detailed Description

A selection committee (composed of minimum two 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 Type: Interventional
• Enrollment (Estimated): 104
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bron, France, 69500
    • Hopital Louis Pradel
  • Dijon, France, 21000
    • Chu Dijon
  • Le Plessis-Robinson, France, 92350
    • Hôpital Marie Lannelongue
  • Lille, France, 59000
    • Centre Hospitalier Régional Universitaire
  • Montpellier, France, 34090
    • CHRU Montpellier
  • Nantes, France, 44093
    • Hopital Laennec
  • Paris, France, 75013
    • Groupe Hospitalier Pitié-Salpêtrière,
  • Paris, France, 75015
    • Hôpital Européen George Pompidou
  • Rennes, France, 35033
    • Hôpital Pontchaillou
  • Strasbourg, France, 67000
    • Nouvel Hôpital Civil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carmat TAH (Cohort 1); Subjects implanted with Carmat TAH	Device: Carmat Total Artificial Heart; Heart Replacement Therapy
Active Comparator: Standard Therapy (cohort 2); Standard Therapy	Other: Standard therapy for heart failure; Other approaches in Bridge to Transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival free of disabling stroke and free of reoperation for device malfunction at 180 days post-implant	Success is defined as survival free of disabling stroke (Modified Rankin score >3) and free of device malfunction leading to a reoperation for device replacement or urgent transplantation, or electively transplanted within 180 days after Carmat TAH implantation	180 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Carmat SAS
• Investigators: Study Director: Frederic C Daoud, MD, PhD, Carmat SAS

Publications and helpful links

General Publications

• Kirklin JK, Xie R, Cowger J, de By TMMH, Nakatani T, Schueler S, Taylor R, Lannon J, Mohacsi P, Gummert J, Goldstein D, Caliskan K, Hannan MM. Second annual report from the ISHLT Mechanically Assisted Circulatory Support Registry. J Heart Lung Transplant. 2018 Jun;37(6):685-691. doi: 10.1016/j.healun.2018.01.1294. Epub 2018 Jan 31.
• Arabia FA, Cantor RS, Koehl DA, Kasirajan V, Gregoric I, Moriguchi JD, Esmailian F, Ramzy D, Chung JS, Czer LS, Kobashigawa JA, Smith RG, Kirklin JK. Interagency registry for mechanically assisted circulatory support report on the total artificial heart. J Heart Lung Transplant. 2018 Nov;37(11):1304-1312. doi: 10.1016/j.healun.2018.04.004. Epub 2018 Apr 26.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2022
• Primary Completion (Actual): October 24, 2025
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: July 14, 2020
• First Submitted That Met QC Criteria: July 14, 2020
• First Posted (Actual): July 17, 2020

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: CAR2019-FR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: European regulation on personal data protection

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No