Prospective Multi-Center Randomized Study for Evaluating the EVAHEART®2 Left Ventricular Assist System

Study Overview
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Brief Summary
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This is a prospective, multi-center, unblinded, randomized, controlled, and non-inferiority study comparing the EVA2 LVAS to the most recent magnetically levitated centrifugal LVAS (HM3 LVAS).

Detailed Description
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Adult (>18 years old), advanced heart failure NYHA Class III with dyspnea upon mild physical activity or Class IV patients who are refractory to advanced heart failure management and meet study Inclusion/Exclusion criteria will be enrolled. The objective of the study is to evaluate the safety and effectiveness of the EVA2 by demonstrating non-inferiority to commercially approved LVADs when used for the treatment of refractory advanced heart failure. Subjects will be followed for 6 months (short-term cohort) and 24 months (long-term cohort) after EVA2/HM3 LVAS implantation or until outcome events of transplantation, explantation, death or withdrawal, whichever occurs first. Whereas subjects experiencing the outcome events of Severe RHF and Disabling stroke will remain in study follow-up.

Official Title
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Prospective Multi-Center Randomized Study for Evaluating the EVAHEART®2 Left Ventricular Assist System: the COMPETENCE Trial

Conditions
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Heart Failure

Intervention / Treatment
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* Device: EVAHEART Left Ventricular Assist System (LVAS)
* Device: HeartMate 3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The following is a list of general inclusion criteria: Age ≥ 18 years Left Ventricular Ejection Fraction (LVEF) < 30% NYHA Class III with dyspnea upon mild physical activity or Class IV heart failure Inotrope dependent OR Cardiac Index (CI) < 2.2 L/min/m2, while not on inotropes Patient is able to provide written informed consent More detailed inclusion criteria information is noted in the study protocol Exclusion Criteria: Etiology of heart failure due to or associated with uncorrected thyroid disease, obstructive cardiomyopathy, pericardial disease, amyloidosis, or restrictive cardiomyopathy Technical obstacles which pose an inordinately high surgical risk Existence of ongoing mechanical circulatory support (MCS) other than IABP and Impella 5.0 or 5.5 Ongoing Impella (5.0 or 5.5) presenting related clinical sign (i.e. hematuria) and elevated LDH equal or greater than 600 IU/L. Positive pregnancy test if of childbearing potential Presence of mechanical aortic cardiac valve that will not be either converted to a bioprosthesis History of any organ transplant Platelet count <100,000/mL Psychiatric disease/disorder, irreversible cognitive dysfunction or psychosocial issues History of confirmed, untreated abdominal aortic aneurysm (AAA) > 5 cm in diameter within 6 months of enrollment Presence of an active, uncontrolled infection Intolerance to anticoagulant or antiplatelet therapies or any other peri/postoperative therapy that the investigator will require based upon the patient's health status Presence of remarkable pre-defined end-organ dysfunction. Patient has moderate to severe aortic insufficiency without plans for correction during pump implant Low albumin - removed from recent exclusion criteria Planned Bi-VAD support prior to enrollment Patient has known hypo- or hyper coagulable state such as disseminated intravascular coagulation and heparin induced thrombocytopenia (HIT) Participation in any other clinical investigation that is likely to confound study results or affect the study Any condition other than heart failure that could limit survival to less than 24 months Patients refusing blood transfusion

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Three-hundred and ninety-nine (399) subjects will be enrolled and randomized in a 2:1 assignment to receive EVA2 or the comparator device, HeartMate 3.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Evaheart LVAS (EVA2)<br>The objective of the study is to evaluate the safety and effectiveness of the EVA2 by demonstrating non-inferiority to commercially approved LVADs when used for the treatment of refractory NYHA Class III with dyspnea upon mild physical activity or Class IV heart failure. | Device: EVAHEART Left Ventricular Assist System (LVAS)<br>* Three-hundred and ninety-nine (399) subjects will be enrolled and randomized in a 2:1 assignment to receive EVA2 or the comparator device, HeartMate 3.<br>* Other names: EVA2;|
| Active Comparator: HeartMate 3 (HM3)<br>The objective of the study is to evaluate the safety and effectiveness of the EVA2 by demonstrating non-inferiority to commercially approved LVADs when used for the treatment of refractory NYHA Class III with dyspnea upon mild physical activity or Class IV heart failure. | Device: HeartMate 3<br>* Three-hundred and ninety-nine (399) subjects will be enrolled and randomized in a 2:1 assignment to receive EVA2 or the comparator device, HeartMate 3.<br>* Other names: HM3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short-Term Primary Endpoint | Survival to cardiac transplant or device explant for recovery free from disabling stroke (Modified Rankin Score > 3) or pre-defined severe Right Heart Failure at 6 months after implantation of the originally implanted device | 6 months | 
| Long-Term Primary Endpoint | Survival to cardiac transplant or device explant for recovery free from disabling stroke (Modified Rankin Score > 3) or pre-defined severe Right Heart Failure at 24 months after implantation of the originally implanted device | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in KCCQ and EuroQol |  | Baseline versus POD 30, 90, 180, 360 and every 180 days | 
| Change in 6-minute walk test |  | Baseline versus POD 30, 90, 180, 360 and every 180 days | 
| NYHA functional class |  | Baseline versus POD 30, 90, 180, 360, and every 180 days | 
| Frequency and incidence of all re-operations |  | Discharge after implant through transplant or explant for recovery. | 
| Frequency and incidence of all rehospitalizations |  | Discharge after implant through transplant or explant for recovery. | 
| Incidence of adverse events, serious adverse events and UADEs | Peri-operative complications and any failure to successfully implant the device. All adverse events occurring during the acute and chronic phase of the study (frequency, severity, duration, sequelae and relationship to device). All adverse events occurring during the extension phase (frequency, severity, duration, sequelae and relationship to device). | Implant through transplant or explant for recovery (+60 days or discharge) or 180 days on device; then duration of device support, up to 360 days (approximate) | 
| Incidence of all device failures and device malfunctions |  | Implant through transplant or explant for recovery (+60 days or discharge) or 180 days on device; then duration of device support, up to 360 days(approximate) | 
| Post-transplant or post-explant survival |  | Up to 30 days post-transplant or post-explant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, LVAS, LVAD, Bridge-to-transplant, Continuous flow pump, Destination therapy