Investigation of the BrioVAD System for the Treatment of Left Ventricular Heart Failure

Investigation of a Novel, magNetically Levitated VAD for the Treatment of refractOry Left Ventricular heArT failurE

The goal of this study is to evaluate the safety and efficacy of the BrioVAD System by demonstrating non-inferiority to the HeartMate 3 Left Ventricular Assist System when used for the treatment of advanced, refractory, left ventricular heart failure.

The INNOVATE Trial is a prospective, non-blinded, randomized, controlled, multi-center, non-inferiority study to evaluate the safety and efficacy of the BrioVAD System by demonstrating non-inferiority to the HeartMate 3™ (HM3) LVAS (Abbott) when used for the treatment of advanced, refractory left ventricular heart failure. It is the first clinical study to compare two left ventricular assist devices (LVAD) that belong to the same category of fully magnetically levitated LVAD.

Inclusion Criteria:

1. Patient is ≥ 18 years of age.

2. Patient has received institutional approval for LVAD implantation.

3. Patient has a body surface area (BSA) ≥ 1.2 m2.

4. Patient is classified as NYHA Class IV with advanced heart failure refractory to advanced heart failure management or NYHA Class III with dyspnea upon mild physical activity.

5. Patient has a left ventricular ejection fraction (LVEF) ≤ 25% or LVEF < 30% on inotropes or temporary MCS.

6. Patient is inotrope dependent, OR has a cardiac index (CI) ≤ 2.2 liters/min/m2, while not on inotropes, and also meets one of the following criteria:

   1. Is on optimal medical management (OMM), based on current heart failure practice guidelines for at least 45 out of the last 60 days and is failing to respond or is not able to tolerate OMM; or
   2. Has advanced heart failure for at least 14 days and is dependent on an intra-aortic balloon pump (IABP) or temporary mechanical circulatory support device (MCSD) for at least seven days.

7. Patient has provided voluntary and informed consent.

8. Females of childbearing age agree to use adequate contraception and have a negative pregnancy test.

Exclusion Criteria:

1. Patient's heart failure etiology is related to restrictive or constrictive physiology (e.g., nondilated hypertrophic cardiomyopathy, cardiac amyloidosis/senile or other infiltrative disease), complex congenital heart disease (e.g., transposition of the great vessels), uncorrected thyroid disease, and/or pericardial disease.

2. Patient had a myocardial infarction within seven days of study enrollment.

3. Patient had cardiothoracic surgery within 30 days of implant with the exception of a procedure to implant temporary MCS: Impella 5.5, Impella CP or TandemHeart.

4. Patient has physiological conditions or comorbidities which pose high surgical risk or obstacles as determined by the Investigator.

5. Patient has contraindications to warfarin anticoagulation.

6. Patient has known hypo- or hypercoagulable state [e.g., disseminated intravascular coagulation (DIC)], or has a positive heparin-induced thrombocytopenia (HIT) assay and positive serotonin release assay or requires use of a non-heparin alternative anticoagulation strategy for cardiopulmonary bypass in the judgement of the Investigator.

7. Patient is on durable MCS (e.g., LVAD or RVAD).

8. Planned need for durable or temporary RVAD support concomitant with LVAD implant.

9. Patient is on any form of pre-implant temporary MCS other than isolated LVAD support with an intra-aortic balloon pump, Impella 5.5, Impella CP, or TandemHeart.

10. Patient is on any form of pre-implant temporary MCS and has a serum lactate dehydrogenase greater than 2.5 times the upper limits of normal or plasma free hemoglobin > 40 g/dL.

11. Patient has a history of organ transplantation.

12. Patient has a mechanical aortic valve that may not be converted to a bioprosthetic valve at the time of VAD implant.

13. Patient has a platelet count < 50 k/μl.

14. Patient has a history of confirmed untreated abdominal aortic aneurysm (AAA) > 5 cm in diameter.

15. Patient has moderate or severe aortic insufficiency that will not be corrected during the VAD implant procedure.

16. Patient has an uncontrolled systemic infection.

17. Patient has a positive COVID 19 test within 21 days of study enrollment and at least one high risk feature including need for supplemental oxygen or ferritin >1000 ug/L.

18. Patient has severe end-organ dysfunction as evidenced by one or more of the following criteria:

    1. Total bilirubin > 3.0 mg/dL or cirrhosis confirmed by liver imaging or hemodynamic assessment with or without biopsy confirmation.
    2. International normalized ratio (INR) ≥ 2.0 or PTT > 2.5 times control that is not related to anticoagulation therapy.
    3. Glomerular filtration rate (GFR) < 30 mL/ min/1.73 m2 or need for renal replacement therapy.
    4. Severe pulmonary arterial hypertension with a pulmonary vascular resistance (PVR) ≥ 8 Wood units that is not acutely reversible with pharmacologic intervention.
    5. Severe chronic obstructive pulmonary disease (COPD) or restrictive lung disease requiring home oxygen or an FEV1/FVC < 0.7 and FEV1 < 40% predicted.
    6. Mechanical ventilation for more than three days present at the time of study enrollment.
    7. Documented history of pulmonary embolism or pulmonary infarct within 60 days of study enrollment.
    8. History of stroke within 90 days of study enrollment or history of stroke with a mRS ≥ 3 at the time of study enrollment.
    9. Symptomatic cerebrovascular disease and/or uncorrected carotid stenosis > 80%.
    10. Significant peripheral vascular disease (PVD) accompanied by pain at rest or extremity ulceration.
    11. Pre-albumin < 15 mg/dL and/or albumin < 2.5 g/dL.

19. Patient has a non-cardiac comorbidity or illness that would limit survival to less than two years.

20. Patient has a psychiatric disease or disorder, or irreversible cognitive dysfunction, and/or insufficient social support or a history of non-adherence with medical instructions that is likely to impair study compliance.

21. Patient is participating in an interventional clinical trial that may impact or confound the results of the INNOVATE Trial.