MOMENTUM 3 IDE Clinical Study Protocol

Study Overview
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Brief Summary
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The objective of the study is to evaluate the safety and effectiveness of the HM3 LVAS by demonstrating non-inferiority to the HMII LVAS (HMII) when used for the treatment of advanced, refractory, left ventricular heart failure.

Detailed Description
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The HM3 LVAS is intended to provide hemodynamic support in patients with advanced, refractory left ventricular heart failure; either for short term support, such as a bridge to cardiac transplantation (BTT) or myocardial recovery, or as long term support, such as destination therapy (DT). The HM3 is intended for use inside or outside the hospital.

Official Title
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Thoratec Corporation MOMENTUM 3, Multi-center Study of MagLev Technology in Patients Undergoing MCS Therapy With HeartMate 3™ IDE Clinical Study Protocol

Conditions
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Advanced Refractory Left Ventricular Heart Failure

Intervention / Treatment
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* Device: HeartMate 3 LVAS
* Device: HeartMate II LVAS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject or legal representative has signed Informed Consent Form (ICF) Age ≥ 18 years BSA ≥ 1.2 m2 NYHA Class III with dyspnea upon mild physical activity, or NYHA Class IV LVEF ≤ 25% a) Inotrope dependent OR b) CI < 2.2 L/min/m2, while not on inotropes and subjects 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 Advanced Heart Failure for at least 14 days AND dependent on intra-aortic balloon pump (IABP) for at least 7 days Females of child bearing age must agree to use adequate contraception Exclusion Criteria: Etiology of heart failure (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 Presence of mechanical aortic valve that will not be either converted to a bioprosthesis or oversewn 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 within 6 months of enrollment 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 ≥ 2.0 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, and 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%) uncorrected carotid stenosis Serum creatinine ≥ 221 umol/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 (15mg/dL) or Albumin < 30g/L (3 g/dL) (if only one available) ; pre albumin < 150 mg/L (15mg/dL) and Albumin < 30g/L (3 g/dL) (if both available) 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
Maximum Age: 100 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HeartMate 3 LVAS (HM3 LVAS)<br>Evaluation of the safety and effectiveness of the HeartMate 3 LVAS by demonstrating non-inferiority to the HMII LVAS (HMII) when used for the treatment of advanced, refractory, left ventricular heart failure. | Device: HeartMate 3 LVAS<br>* Implantation of HeartMate 3 LVAD to evaluate the safety and effectiveness of the HeartMate 3 LVAS by demonstrating non-inferiority to the HMII LVAS (HMII) when used for the treatment of advanced, refractory, left ventricular heart failure<br>|
| Active Comparator: HeartMate II LVAS<br>Evaluation of the safety and effectiveness of the HeartMate 3 LVAS by demonstrating non-inferiority to the HMII LVAS (HMII) when used for the treatment of advanced, refractory, left ventricular heart failure. | Device: HeartMate II LVAS<br>* Implantation of the commercially approved HeartMate II LVAD which is the standard treatment for advanced heart failure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short Term Primary End Point | Survival at 6 months free of disabling stroke (Modified Rankin Score > 3) or reoperation to replace or remove a malfunctioning device | The first 294 randomized Subjects will be followed for 6 months or to outcome (transplant, explant, or death), whichever occurs first. | 
| Long Term Primary End Point | Survival at 2 years free of disabling stroke (Modified Rankin Score > 3) or reoperation to replace or remove a malfunctioning device | The first 366 randomized Subjects will be followed for 24 months or to outcome (transplant, explant, or death), whichever occurs first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Powered Secondary End Point: Pump Replacement at Two Years | In addition to powering the study on the primary endpoints for PMA approval, the study will pre-specify a powered secondary endpoint to evaluate incidence of pump replacements at 24 months. HeartMate II is the control. | As they occur up to 24 months or to Outcome, whichever occurs first | 
| EuroQoL 5D-5L (EQ-5D-5L) Total Score | Quality of Life as measured by EuroQoL 5 Dimension-5 Level (EQ-5D-5L) total score. The EQ-5D-5L questionnaire has patients rate their quality of life across 5 categories of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The scores from the 5 dimensions are summed for the total score which ranges from 5 to 25 with higher scores indicating more problems and a worse quality of life. | Baseline to 24 months | 
| EuroQol-5D-5L Visual Analogue Scale | Quality of life as measured by the visual analogue scale from the EuroQol-5D-5L questionnaire. The patient rates their current state of health with the visual analogue scale. The scale ranges from 0 to 100. Higher scores indicate a better quality of life. | Baseline to 24 months | 
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | Quality of Life as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Scores range from 0 to 100. Higher scores indicate better quality of life and fewer heart failure symptoms. | Baseline to 24 months | 
| Six Minute Walk Test | Functional status as measured by the Six Minute Walk Test. The Six Minute Walk Test measures the distance a patient is able to walk during 6 minutes without running or jogging. | Baseline to 24 months | 
| New York Heart Association (NYHA) Classification | Functional status as measured by NYHA classification. NYHA class categorizes patients by the severity of their heart failure symptoms. As the class increases, the degree of symptoms is more severe indicating worse functional status. Class I indicates no limitation of physical activity. Class II indicates slight limitation of physical activity. Class IIIA indicates marked limitation of physical activity where less than ordinary physical activity causes fatigue, palpitation, dyspnea, or angina pain. Class IIIB indicates marked limitation of physical activity where mild physical activity causes fatigue, palpitation, dyspnea, or angina pain. Class IV indicates inability to carry on any physical activity without discomfort. | Baseline to 24 months | 
| Rehospitalizations | Rate of all cause rehospitalization | From initial discharge to two years post-implant | 
| Adverse Event Rates | Events-per-patient-year (EPPY) for anticipated adverse events as defined in the study protocol | Two years post-implant | 

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