European Clinical Evaluation of the Carmat Total Artificial Heart

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Clinical Evaluation of the Carmat Total Artificial Heart for Patients With Advanced Heart Failure

Conditions
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Advanced Heart Failure

Intervention / Treatment
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* Device: CARMAT TAH
* Procedure: Surgical intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient age: 18 to 75 years Inotrope dependent or cardiac Index (CI) < 2.2 L/min/m2 if inotropes are contra-indicated (heart failure due to restrictive or constrictive physiology). On Optimal Medical Management as judged by the investigator based on current Heart Failure practice guidelines (ESC/AHA) Eligible to biventricular Mechanical Circulatory Support according to ISHLT guidelines for mechanical circulatory support: Biventricular failure with at least two of the following hemodynamic/ echocardiographic measurements implying right heart failure: RVEF ≤ 30% RVSWI ≤ 0.25 mmHg*L/m2 TAPSE ≤ 14mm RV-to-LV end-diastolic diameter ratio > 0.72 CVP > 15 mmHg CVP-to-PCWP ratio > 0.63 Tricuspid insufficiency grade 4 Treatment-refractory recurrent and sustained ventricular tachycardia or ventricular fibrillation in the presence of untreatable arrhythmogenic pathologic substrate Heart failure due to restrictive or constrictive physiology (e.g., hypertrophic cardiomyopathy, cardiac amyloidosis / senile or other infiltrative heart disease) Anatomic compatibility confirmed using 3D imaging (CT-scan) Patient's affiliation to health care insurance, if local requirement Patient has signed the informed consent and committed to follow study requirements Exclusion Criteria: Body Mass Index (BMI) < 15 or > 47 Existence of any ongoing non-temporary mechanical circulatory support Existence of any temporary mechanical circulatory support other than IABP and Impella History of cardiac or other organ transplant Patients who have required cardiopulmonary resuscitation for > 30 minutes within 14 days prior to implant Known intolerance to anticoagulant or antiplatelet therapies Coagulopathy defined by platelets < 100k/μl or INR ≥ 1.5 not due to anticoagulant therapy Cerebro-vascular accident < 3 months or symptomatic or a known > 80% carotid stenosis Known abdominal or thoracic aortic aneurysm > 5 cm End-organ dysfunction as per investigator judgment and following but not limited criteria: Total bilirubin > 100 μmol/L (5,8 mg/dl) or cirrhosis evidenced by ultrasound, CT-scan or positive biopsy GFR < 30ml/min/1.73m2 History of severe Chronic Obstructive Pulmonary Disease or severe restrictive lung disease Recent blood stream infection (<7 days) Documented amyloid light-chain (AL amyloidosis) Hemodynamically significant peripheral vascular disease accompanied by rest pain or extremity ulceration Illness, other than heart disease, that would limit survival to less than 1 year Irreversible cognitive dysfunction, psychosocial issues or psychiatric disease, likely to impair compliance with the study protocol and TAH management Participation in any other clinical investigation that is likely to confound study results or affect the study Pregnancy or breast feeding (woman in age of childbearing will have to show negative pregnancy test)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carmat TAH<br>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<br> <br> Procedure: Surgical intervention<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with survival at 180 days | Success is defined as survival at 180 days after Carmat TAH implantation or transplanted if before 180 days. | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Patient follow-up | 180 days | 
| General health status change (1) | 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. | 180 days | 
| General health status change (2) | 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. | 180 days | 
| Functional status change | New York Heart Association (NYHA) functional classification (regression scale I, II, III, IV) | 180 days | 
| 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 | 
| Adverse events | Adverse Event Rates will be captured per the INTERMACS definitions | 180 days | 
| hospital readmission rate | 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 | 180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced heart failure, Total artificial heart