Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device (LVAD) and Medical Management

Study Overview
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Brief Summary
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The purpose of this study is to evaluate and compare the effectiveness of the HeartMate II (HM II) Left Ventricular Assist Device (LVAD) support versus OMM in ambulatory NYHA Class IIIB/IV heart failure patients who are not dependent on intravenous inotropic support and who meet the FDA approved indications for HM II LVAD destination therapy.

Detailed Description
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The HeartMate II (HM II) LVAD is approved by the U.S. Food and Drug Administration (FDA) for use in destination therapy (DT) patients with New York Heart Association (NYHA) Class IIIB/IV symptoms. The ROADMAP trial is a prospective, multi-center, non-randomized, controlled, observational study that is designed to evaluate the effectiveness of HM II LVAD support versus optimal medical management (OMM) in ambulatory NYHA Class IIIB/IV heart failure patients who are not dependent on intravenous inotropic support and who meet the FDA approved indications for HM II LVAD destination therapy. Subjects will be enrolled in one of two cohorts: OMM or LVAD. Together with the investigator, the subjects will decide which cohort to enter into at their baseline visit. This study will include experienced HM II LVAD implant centers as well as community centers that care for a large volume of heart failure patients. Study patients will be followed for up to 24 months post enrollment for survival, quality of life and functional status.

Official Title
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Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients

Conditions
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Heart Failure

Intervention / Treatment
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* Device: HM II (HeartMate II LVAD)
* Drug: OMM (Optimal Medical Management)


Participation Criteria
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Eligibility Criteria
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The following are general criteria; more specific criteria are included in the study protocol: Inclusion Criteria: NYHA Class IIIB/IV (refer to Appendix IV for definitions) Left ventricular ejection fraction (LVEF) ≤ 25% Not currently listed for heart transplantation, and not planned in next 12 months On optimal medical management Limited functional status as demonstrated by 6MWT <300 meters At least: One hospitalization for HF in last 12 months or At least 2 unscheduled emergency room or infusion clinic visits (may include intravenous diuretic therapy, etc.) for HF in last 12 months Exclusion Criteria: Presence of mechanical aortic or mitral valve, including planned conversion to bioprosthesis Platelet count < 100,000/mi within 48 prior to enrollment Any inotrope use within 30 days prior to enrollment Inability to perform 6MWT for any reason Any condition, other than heart failure, that could limit survival to less than 2 years History of cardiac or other organ transplant Existence of any ongoing mechanical circulatory support (including intraaortic balloon pump, temporary circulatory support devices, etc.) at the time of enrollment Presence of active, uncontrolled, systemic infection History of an unresolved stroke within 90 days prior to enrollment, or a history of cerebral vascular disease with significant (> 80%)extracranial stenosis Contraindication to anticoagulation/antiplatelet therapy CRT or CRT-D within 3 months prior to enrollment Coronary revascularization (e.g. CABG, PCI) within 3 months prior to enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HM II (HeartMate II LVAD)<br>Subjects who elect to, and receive HM II LVAD therapy at baseline | Device: HM II (HeartMate II LVAD)<br>* The HM II pump contains a single moving component, the rotor. The pump is implanted just below the left hemidiaphragm with the inflow attached to the apex of the left ventricle and the outflow graft anastomosed to the ascending aorta. Blood is pumped continuously throughout the cardiac cycle from the left ventricle to the aorta.<br>* Other names: Left Ventricular Assist Device;|
| OMM (Optimal Medical Management)<br>Subjects who elect to remain on optimal medical management | Drug: OMM (Optimal Medical Management)<br>* Optimal medical management per established heart failure guidelines for this subject population including ACE inhibitors, beta blockers and aldosterone antagonists 45 out of the last 60 days or an inability to tolerate neurohormonal antagonists.<br>* Other names: Medical Management;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of survival with improvement in Six Minute Hallway Walk Test distance from baseline of ≥ 75m. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk stratified subgroup analysis of the primary endpoint and temporal analysis of primary endpoint. |  | 6, 12, 18, and 24 months | 
| Accuracy of prognostic survival risk models including Seattle Heart Failure Model (SHFM) and HeartMate II Risk Score (HMRS) |  | Baseline and 6, 12, 18 and 24 months | 
| Actuarial survival and survival free of stroke: a) intent-to-treat; and b) as treated. |  | 24 months | 
| Survival in LVAD group free of pump replacement. |  | 24 months | 
| Quality of Life using the EQ-5D-5L Health Utility Index. |  | Baseline and 6, 12, 18 and 24 months | 
| Depression using Patient Health Questionnaire-9 (PHQ-9). |  | Baseline and 6, 12, 18 and 24 months | 
| Questionnaire on patient decisions related to LVAD therapy versus optimal medical management. |  | Baseline and 6, 12, 18 and 24 months | 
| Functional status using 6MWT distance and NYHA Classification |  | Baseline and 6, 12, 18 and 24 months | 
| Incidence of adverse events, rehospitalizations, days alive and not hospitalized. |  | 3, 6, 9, 12, 15, 18, 21 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HeartMate II, heart-assist device, medical management, optimal medical management, Heart Failure NYHA Class IIIB/IV, Thoratec Corporation