HeartMate 3™ CE Mark Clinical Investigation Plan

HeartMate 3™ CE Mark Clinical Investigation Plan

The purpose of this clinical investigation is to evaluate the performance and safety of the HeartMate 3 Left Ventricular Assist System (HM3 LVAS) To support obtaining CE Mark for the HM3 LVAS in Europe, a multi-center clinical study will be conducted in multiple countries. The clinical study will be conducted in compliance with the Declaration of Helsinki, ICH/GCP and EN ISO 14155:2011 Requirements for Clinical Investigations and in accordance with country-specific requirements, under one clinical study protocol.

This study will evaluate the performance of the HM3 LVAS, side effects and undesirable conditions within acceptable risks and weigh them against the intended performance of HM3 LVAS in accordance with Essential Requirements 2, 5 and 16 of the Active Implantable Medical Device Directive 90/385/EEC (AIMDD).

Inclusion Criteria:

1. Patient or legal representative has signed Informed Consent Form (ICF)

2. Age ≥ 18 years

3. BSA ≥ 1.2 m2

4. NYHA IIIB or IV OR ACC/AHA Stage D

5. LVEF ≤ 25%

6. CI ≤ 2.2 L/min/m2, while not on inotropes

7. Patients must also meet one of the following:

   - On Optimal Medical Management (OMM), based on current heart failure practice guidelines for at least 45 out of the last 60 days and are failing to respond,

   OR

   - In NYHA class IIIB or IV heart failure for at least 14 days AND dependent on intraaortic balloon pump (IABP) for at least 7 days,

   OR

   - Inotrope dependent/unable to wean from inotropes

   OR

   - Listed for Transplant

8. Females of child bearing age must agree to use adequate contraception

Exclusion Criteria:

1. Etiology of HF due to or associated with uncorrected thyroid disease, obstructive cardiomyopathy, pericardial disease, amyloidosis or restrictive cardiomyopathy

2. Technical obstacles which pose an inordinately high surgical risk, in the judgment of the investigator

3. Existence of ongoing mechanical circulatory support (MCS) other than IABP

4. Positive pregnancy test if of childbearing potential

5. Lactating mothers

6. Presence of mechanical aortic cardiac valve that will not be converted to a bioprosthesis at the time of LVAD implant

7. History of any organ transplant

8. Platelet count < 100,000 x 103/L (< 100,000/ml)

9. Psychiatric disease/disorder, irreversible cognitive dysfunction or psychosocial issues that are likely to impair compliance with the study protocol and LVAS management

10. History of confirmed, untreated AAA > 5 cm in diameter

11. Presence of an active, uncontrolled infection

12. Intolerance to anticoagulant or antiplatelet therapies or any other peri/post-operative therapy the investigator will require based upon the patients' health status

13. Presence of any one of the following risk factors for indications of severe end organ dysfunction or failure:

    1. An INR ≥ 2.5 not due to anticoagulation therapy
    2. Total bilirubin > 43 umol/L (2.5 mg/dl), shock liver, or biopsy proven liver cirrhosis
    3. History of severe chronic obstructive pulmonary disease (COPD) defined by FEV1/FVC < 0.7, or FEV1 <50% predicted
    4. Fixed pulmonary hypertension with a most recent PVR ≥ 8 Wood units that is unresponsive to pharmacologic intervention
    5. History of stroke within 90 days prior to enrollment, or a history of cerebrovascular disease with significant (> 80%) carotid artery stenosis
    6. Serum creatinine ≥221umol/L (2.5 mg/dl) or the need for chronic renal replacement therapy
    7. Significant peripheral vascular disease (PVD) accompanied by rest pain or extremity ulceration

14. Patient has moderate to severe aortic insufficiency without plans for correction during pump implant

15. Pre albumin < 150 mg/L, or Albumin < 30g/L (3 g/dL)

16. Planned Bi-VAD support prior to enrollment

17. Patient has known hypo or hyper coagulable states such as disseminated intravascular coagulation and heparin induced thrombocytopenia

18. Participation in any other clinical investigation that is likely to confound study results or affect the study

19. Any condition other than HF that could limit survival to less than 24 months