European Clinical Evaluation of the Carmat Total Artificial Heart (ADVANCEHF)

• ClinicalTrials.gov Identifier: NCT02962973
• Recruitment Status: Suspended
• First Posted: November 15, 2016
• Last Update Posted: February 8, 2023
• Sponsor: Carmat SA
• Information provided by (Responsible Party): Carmat SA

Study Description

Brief Summary:

The objective of this clinical investigation is to evaluate the safety and performance of the Carmat Total Artificial Heart (TAH) in subjects with advanced heart failure requiring biventricular support.

Each subject receiving the Carmat TAH will be evaluated at 6 months (180 days) for primary and secondary endpoints with further follow-up assessments up to 2 years.

The results of the study will be used to support a CE mark application.

Condition or disease	Intervention/treatment	Phase
Advanced Heart Failure	Device: CARMAT TAH; Procedure: Surgical intervention	Not Applicable

Detailed Description:

Center selection is based on the following: experience with VAD/TAH implantation and record of good results in this patient population (% of survival), the infrastructure required to perform the clinical investigation (especially the surgical and cardiology teams); site resources and experience to manage the clinical study and the patient population; the adherence to the standards of Good Clinical Practice. A specific focus during the site selection is done on dedicated VAD - nurse team to ensure that:

• Sites are experienced in the selection of patients whom require a mechanical circulatory support. Social and psychological conditions of the patient and family must be considered to ensure patient and family commitment in the care pathway,
• Close supervision of patients on the use of the device (when changing batteries) by experienced hospital professionals is guarantee;
• Extensive hospital training program and regular support for patients and family - relatives are ensured.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Evaluation of the Carmat Total Artificial Heart for Patients With Advanced Heart Failure
• Actual Study Start Date: September 2016
• Estimated Primary Completion Date: December 2023
• Estimated Study Completion Date: July 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Carmat TAH; The surgical intervention takes place through a midsternotomy utilizing cardiopulmonary bypass. The device is then connected via a percutaneous driveline to an external controller and batteries and takes over the circulation.	Device: CARMAT TAH; Procedure: Surgical intervention

Outcome Measures

Primary Outcome Measures :

1. Proportion of participants with survival at 180 days [ Time Frame: 180 days ]
   Success is defined as survival at 180 days after Carmat TAH implantation or transplanted if before 180 days.

Secondary Outcome Measures :

1. Overall survival [ Time Frame: 180 days ]
   Patient follow-up
2. General health status change (1) [ Time Frame: 180 days ]
   Measured with the EuroQol EQ-5D questionnaire, a descriptive system of health-related quality of life states 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.
3. General health status change (2) [ Time Frame: 180 days ]
   Change as measured by the SF-36 questionnaire, consisting of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.
4. Functional status change [ Time Frame: 180 days ]
   New York Heart Association (NYHA) functional classification (regression scale I, II, III, IV)
5. Change in functional status measured by the Six Minutes Walk Test [ Time Frame: 180 days ]
   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.
6. Adverse events [ Time Frame: 180 days ]
   Adverse Event Rates will be captured per the INTERMACS definitions
7. hospital readmission rate [ Time Frame: 180 days ]

   Rate of unplanned readmissions to the hospital

   • Frequency and incidence of all adverse events
   • Frequency and incidence of pre-defined anticipated adverse events
   • Frequency, incidence and type of device malfunction

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patient age: 18 to 75 years
2. Inotrope dependent or cardiac Index (CI) < 2.2 L/min/m2 if inotropes are contra-indicated (heart failure due to restrictive or constrictive physiology).
3. On Optimal Medical Management as judged by the investigator based on current Heart Failure practice guidelines (ESC/AHA)

4. Eligible to biventricular Mechanical Circulatory Support according to ISHLT guidelines for mechanical circulatory support:

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

      1. RVEF ≤ 30%
      2. RVSWI ≤ 0.25 mmHg*L/m2
      3. TAPSE ≤ 14mm
      4. RV-to-LV end-diastolic diameter ratio > 0.72
      5. CVP > 15 mmHg
      6. CVP-to-PCWP ratio > 0.63
      7. 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)
5. Anatomic compatibility confirmed using 3D imaging (CT-scan)
6. Patient's affiliation to health care insurance, if local requirement
7. Patient has signed the informed consent and committed to follow study requirements

Exclusion Criteria:

1. Body Mass Index (BMI) < 15 or > 47
2. Existence of any ongoing non-temporary mechanical circulatory support
3. Existence of any temporary mechanical circulatory support other than IABP and Impella
4. History of cardiac or other organ transplant
5. Patients who have required cardiopulmonary resuscitation for > 30 minutes within 14 days prior to implant
6. Known intolerance to anticoagulant or antiplatelet therapies
7. Coagulopathy defined by platelets < 100k/μl or INR ≥ 1.5 not due to anticoagulant therapy
8. Cerebro-vascular accident < 3 months or symptomatic or a known > 80% carotid stenosis
9. Known abdominal or thoracic aortic aneurysm > 5 cm

10. End-organ dysfunction as per investigator judgment and following but not limited criteria:

    1. Total bilirubin > 100 μmol/L (5,8 mg/dl) or cirrhosis evidenced by ultrasound, CT-scan or positive biopsy
    2. GFR < 30ml/min/1.73m2
11. History of severe Chronic Obstructive Pulmonary Disease or severe restrictive lung disease
12. Recent blood stream infection (<7 days)
13. Documented amyloid light-chain (AL amyloidosis)
14. Hemodynamically significant peripheral vascular disease accompanied by rest pain or extremity ulceration
15. Illness, other than heart disease, that would limit survival to less than 1 year
16. Irreversible cognitive dysfunction, psychosocial issues or psychiatric disease, likely to impair compliance with the study protocol and TAH management
17. Participation in any other clinical investigation that is likely to confound study results or affect the study
18. Pregnancy or breast feeding (woman in age of childbearing will have to show negative pregnancy test)

Contacts and Locations

Locations

Czechia

Institute for Clinical and Experimental Medicine

Prague, Czechia, 140 21

Denmark

Righospitalet,

Copenhagen, Denmark

France

Service de Chirurgie Cardiaque - Institut Cœur Poumon

Lille, France, 59037

CHU Pontchaillou Centre Cardio-Pneumologie

Rennes, France, 35033

Kazakhstan

"National Research Cardiac Surgery Center"

Astana, Kazakhstan, 010000

Sponsors and Collaborators

Carmat SA

Investigators

• Study Director: Piet Jansen, MD, PhD; Carmat SA

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Netuka I, Pya Y, Bekbossynova M, Ivak P, Konarik M, Gustafsson F, Smadja DM, Jansen P, Latremouille C. Initial bridge to transplant experience with a bioprosthetic autoregulated artificial heart. J Heart Lung Transplant. 2020 Dec;39(12):1491-1493. doi: 10.1016/j.healun.2020.07.004. Epub 2020 Jul 14. No abstract available.

Bizouarn P, Roussel JC, Trochu JN, Perles JC, Latremouille C. Effects of pre-load variations on hemodynamic parameters with a pulsatile autoregulated artificial heart during the early post-operative period. J Heart Lung Transplant. 2018 Jan;37(1):161-163. doi: 10.1016/j.healun.2017.06.018. Epub 2017 Jul 8. No abstract available.

• Responsible Party: Carmat SA
• ClinicalTrials.gov Identifier: NCT02962973
• Other Study ID Numbers: CAR2016-01; CIV-FR-16-09-016865 ( Other Identifier: EUDAMED )
• First Posted: November 15, 2016
• Last Update Posted: February 8, 2023
• Last Verified: February 2023

Keywords provided by Carmat SA:

Advanced heart failure; Total artificial heart

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases