HeartMate 3™ CE Mark Clinical Investigation Plan

Study Overview
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Brief Summary
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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).

Official Title
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HeartMate 3™ CE Mark Clinical Investigation Plan

Conditions
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Advanced Refractory Left Ventricular Heart Failure

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient or legal representative has signed Informed Consent Form (ICF) Age ≥ 18 years BSA ≥ 1.2 m2 NYHA IIIB or IV OR ACC/AHA Stage D LVEF ≤ 25% CI ≤ 2.2 L/min/m2, while not on inotropes 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 Females of child bearing age must agree to use adequate contraception Exclusion Criteria: Etiology of HF 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, in the judgment of the investigator Existence of ongoing mechanical circulatory support (MCS) other than IABP Positive pregnancy test if of childbearing potential Lactating mothers Presence of mechanical aortic cardiac valve that will not be converted to a bioprosthesis at the time of LVAD implant History of any organ transplant Platelet count < 100,000 x 103/L (< 100,000/ml) Psychiatric disease/disorder, irreversible cognitive dysfunction or psychosocial issues that are likely to impair compliance with the study protocol and LVAS management History of confirmed, untreated AAA > 5 cm in diameter Presence of an active, uncontrolled infection Intolerance to anticoagulant or antiplatelet therapies or any other peri/post-operative therapy the investigator will require based upon the patients' health status Presence of any one of the following risk factors for indications of severe end organ dysfunction or failure: An INR ≥ 2.5 not due to anticoagulation therapy Total bilirubin > 43 umol/L (2.5 mg/dl), shock liver, or biopsy proven liver cirrhosis History of severe chronic obstructive pulmonary disease (COPD) defined by FEV1/FVC < 0.7, or FEV1 <50% predicted Fixed pulmonary hypertension with a most recent PVR ≥ 8 Wood units that is unresponsive to pharmacologic intervention History of stroke within 90 days prior to enrollment, or a history of cerebrovascular disease with significant (> 80%) carotid artery stenosis Serum creatinine ≥221umol/L (2.5 mg/dl) or the need for chronic renal replacement therapy Significant peripheral vascular disease (PVD) accompanied by rest pain or extremity ulceration Patient has moderate to severe aortic insufficiency without plans for correction during pump implant Pre albumin < 150 mg/L, or Albumin < 30g/L (3 g/dL) Planned Bi-VAD support prior to enrollment Patient has known hypo or hyper coagulable states such as disseminated intravascular coagulation and heparin induced thrombocytopenia Participation in any other clinical investigation that is likely to confound study results or affect the study Any condition other than HF that could limit survival to less than 24 months

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HeartMate 3<br>Left Ventricular Assist System (LVAS) to be used on Subjects with advanced refractory left ventricular heart failure | Device: Left Ventricular Assist System (LVAS)<br>* Implantation of left ventricular assist device for hemodynamic support<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Comparison of survival at 6 months of Left Ventricular Assist Device (LVAD) support to a performance goal established using matched HeartMate II INTERMACS data | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life (EQ-5D-5L) | The EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group. Patients describe their perceived health status using an analog scale with 0 as the worst health the patient can imagine and 100 as the best health (Visual Analog Score). The patients' scores at one, three and six months were compared to their baseline scores and the resulting positive scores indicated improved quality of life. | Baseline, Month 1, Month 3, Month 6 | 
| Functional Status - Six Minute Walk Test (6MWT) | The Six Minute Walk Test(6MWT)measures the distance that a patient can walk in a period of 6 minutes. The distance walked is measured in meters. This test measures the patients' functional status. The more meters a patient can walk over baseline indicates improvement in functional status. | Baseline, Month 1, Month 3, Month 6 | 
| Functional Status - New York Heart Association (NYHA) Classification | NYHA classification relates symptoms to every day activities and patients quality of life. Class 1 = no limitations on physical activity Class 2 - slight limitation of physical activity Class 3 - marked limitation of physical activity Class 4 = unable to carry out any physical activity without discomfort | Baseline, Month 1, Month 3, Month 6 | 
| All Adverse Events | Frequency of pre-defined anticipated adverse events | As they occurred, Baseline through 180 Days | 
| Device Malfunctions | Frequency and incidence of device malfunction | As they occurred, Baseline through 180 Days; Subjects that remain ongoing after 6 months will continue to be followed to 24 months post-implant or outcome | 
| Reoperations | Frequency of reoperations | As they occurred, Baseline through 180 Days | 
| Rehospitalizations | Frequency and incidence of rehospitalizations | As they occurred, Baseline through 180 Days | 
| Stroke Free Survival | Percentage of participants free of debilitating stroke (Modified Rankin Score > 3) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Ventricular Dysfunction, Cardiomyopathies, Heart Disease, Cardiovascular Disease, Heart-assist devices, Thoratec Corporation