Advanced Refractory Left Ventricular Heart Failure
Conditions
Keywords
Heart Failure, Left Ventricular Assist Device, Ventricular Dysfunction, Cardiomyopathy, Heart Disease, Cardiovascular Disease, Heart-assist devices, Thoratec Corporation
Brief summary
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
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.
Interventions
DEVICEHeartMate 3 LVAS
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
DEVICEHeartMate II LVAS
Implantation of the commercially approved HeartMate II LVAD which is the standard treatment for advanced heart failure
Sponsors
Thoratec Corporation
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Subject or legal representative has signed Informed Consent Form (ICF) 2. Age ≥ 18 years 3. BSA ≥ 1.2 m2 4. NYHA Class III with dyspnea upon mild physical activity, or NYHA Class IV 5. LVEF ≤ 25% 6. 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 7. Females of child bearing age must agree to use adequate contraception
Exclusion criteria
1. Etiology of heart failure (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. Presence of mechanical aortic valve that will not be either converted to a bioprosthesis or oversewn at the time of LVAD implant 6. History of any organ transplant 7. Platelet count \< 100,000 x 103/L (\< 100,000/ml) 8. Psychiatric disease/disorder, irreversible cognitive dysfunction or psychosocial issues that are likely to impair compliance with the study protocol and LVAS management 9. History of confirmed, untreated AAA \> 5 cm in diameter within 6 months of enrollment 10. Presence of an active, uncontrolled infection 11. Intolerance to anticoagulant or antiplatelet therapies or any other peri/post-operative therapy the investigator will require based upon the patients' health status 12. Presence of any one of the following risk factors for indications of severe end organ dysfunction or failure: 1. An INR ≥ 2.0 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, and 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%) uncorrected carotid stenosis 6. Serum creatinine ≥ 221 umol/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 13. Patient has moderate to severe aortic insufficiency without plans for correction during pump implant 14. 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) 15. Planned Bi-VAD support prior to enrollment 16. Patient has known hypo or hyper coagulable states such as disseminated intravascular coagulation and heparin induced thrombocytopenia 17. Participation in any other clinical investigation that is likely to confound study results or affect the study 18. Any condition other than HF that could limit survival to less than 24 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Short Term Primary End Point | The first 294 randomized Subjects will be followed for 6 months or to outcome (transplant, explant, or death), whichever occurs first. | Survival at 6 months free of disabling stroke (Modified Rankin Score \> 3) or reoperation to replace or remove a malfunctioning device |
| Long Term Primary End Point | The first 366 randomized Subjects will be followed for 24 months or to outcome (transplant, explant, or death), whichever occurs first. | Survival at 2 years free of disabling stroke (Modified Rankin Score \> 3) or reoperation to replace or remove a malfunctioning device |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EuroQol-5D-5L Visual Analogue Scale | Baseline to 24 months | 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. |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | Baseline to 24 months | 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. |
| Six Minute Walk Test | Baseline to 24 months | 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. |
| Powered Secondary End Point: Pump Replacement at Two Years | As they occur up to 24 months or to Outcome, whichever occurs first | 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. |
| Rehospitalizations | From initial discharge to two years post-implant | Rate of all cause rehospitalization |
| Adverse Event Rates | Two years post-implant | Events-per-patient-year (EPPY) for anticipated adverse events as defined in the study protocol |
| New York Heart Association (NYHA) Classification | Baseline to 24 months | 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. |
| EuroQoL 5D-5L (EQ-5D-5L) Total Score | Baseline to 24 months | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited at 69 study sites in the United States from 2014 to 2016.
Participants by arm
| Arm | Count |
|---|---|
| HeartMate II (Intent-to-Treat) Patients randomized to HeartMate II LVAS (control device) | 512 |
| HeartMate 3 (Intent-to-Treat) Patients randomized to HeartMate 3 LVAS | 516 |
| Total | 1,028 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomization to Device Implant | Withdrawn prior to implant | 7 | 1 |
| Two Year Follow up Post-implant | Death | 103 | 98 |
| Two Year Follow up Post-implant | Device explant or permanent deactivation | 3 | 3 |
| Two Year Follow up Post-implant | Heart transplant | 137 | 119 |
| Two Year Follow up Post-implant | Withdrawn post-implant | 15 | 6 |
Baseline characteristics
| Characteristic | HeartMate II (Intent-to-Treat) | HeartMate 3 (Intent-to-Treat) | Total |
|---|---|---|---|
| Age, Continuous | 60 years STANDARD_DEVIATION 12 | 59 years STANDARD_DEVIATION 12 | 60 years STANDARD_DEVIATION 12 |
| History of Atrial Fibrillation | 238 Participants | 215 Participants | 453 Participants |
| History of Stroke | 56 Participants | 50 Participants | 106 Participants |
| Implantable cardioverter-defibrillator | 382 Participants | 352 Participants | 734 Participants |
| Inotropes | 423 Participants | 445 Participants | 868 Participants |
| Intended Goal of Support Bridge to candidacy for transplantation | 81 Participants | 86 Participants | 167 Participants |
| Intended Goal of Support Bridge to transplantation | 121 Participants | 113 Participants | 234 Participants |
| Intended Goal of Support Destination therapy | 310 Participants | 317 Participants | 627 Participants |
| INTERMACS profile 1 | 18 Participants | 11 Participants | 29 Participants |
| INTERMACS profile 2 | 146 Participants | 156 Participants | 302 Participants |
| INTERMACS profile 3 | 251 Participants | 272 Participants | 523 Participants |
| INTERMACS profile 4 | 82 Participants | 67 Participants | 149 Participants |
| INTERMACS profile 5-7 or not provided | 15 Participants | 10 Participants | 25 Participants |
| Intra-aortic balloon pump | 79 Participants | 64 Participants | 143 Participants |
| Ischemic Cause of Heart Failure | 240 Participants | 216 Participants | 456 Participants |
| Race/Ethnicity, Customized Race or ethnic group Asian | 3 Participants | 8 Participants | 11 Participants |
| Race/Ethnicity, Customized Race or ethnic group Black | 120 Participants | 145 Participants | 265 Participants |
| Race/Ethnicity, Customized Race or ethnic group Native Hawaiian or Pacific Islander | 4 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Race or ethnic group Other | 18 Participants | 21 Participants | 39 Participants |
| Race/Ethnicity, Customized Race or ethnic group White | 367 Participants | 342 Participants | 709 Participants |
| Sex: Female, Male Female | 93 Participants | 105 Participants | 198 Participants |
| Sex: Female, Male Male | 419 Participants | 411 Participants | 830 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 103 / 505 | 98 / 515 |
| other Total, other adverse events | 235 / 505 | 261 / 515 |
| serious Total, serious adverse events | 466 / 505 | 483 / 515 |
Outcome results
Primary
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
Time frame: The first 366 randomized Subjects will be followed for 24 months or to outcome (transplant, explant, or death), whichever occurs first.
Population: First 366 randomized Subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HeartMate II (Intent-to-Treat) | Long Term Primary End Point | 106 Participants |
| HeartMate 3 (Intent-to-Treat) | Long Term Primary End Point | 151 Participants |
p-value: <0.001Farrington-Manning risk difference
Primary
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
Time frame: The first 294 randomized Subjects will be followed for 6 months or to outcome (transplant, explant, or death), whichever occurs first.
Population: First 294 randomized Subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HeartMate II (Intent-to-Treat) | Short Term Primary End Point | 109 Participants |
| HeartMate 3 (Intent-to-Treat) | Short Term Primary End Point | 131 Participants |
p-value: <0.001Farrington-Manning risk difference
Secondary
Adverse Event Rates
Events-per-patient-year (EPPY) for anticipated adverse events as defined in the study protocol
Time frame: Two years post-implant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Stroke | 0.18 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Right Heart Failure | 0.23 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Arterial Non-CNS Thromboembolism | 0.02 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Bleeding | 0.95 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Cardiac Arrhythmia | 0.45 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Hepatic Dysfunction | 0.04 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Hypertension | 0.08 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Major Infection | 0.82 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Myocardial Infarction | 0.01 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Hemorrhagic Stroke | 0.07 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Ischemic Stroke | 0.11 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Debilitating Stroke | 0.07 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Other Neurological Event | 0.08 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Pericardial Fluid Collection | 0.07 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Psychiatric Episode | 0.07 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Renal Dysfunction | 0.08 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Respiratory Failure | 0.17 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | RVAD | 0.03 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Venous Thromboembolism | 0.04 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Wound Dehiscence | 0.02 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Suspected Device Thrombosis | 0.12 events per patient year |
| HeartMate II (Intent-to-Treat) | Adverse Event Rates | Hemolysis | 0.01 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Debilitating Stroke | 0.04 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Wound Dehiscence | 0.01 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Other Neurological Event | 0.09 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Arterial Non-CNS Thromboembolism | 0.01 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | RVAD | 0.03 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Bleeding | 0.61 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Pericardial Fluid Collection | 0.04 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Cardiac Arrhythmia | 0.37 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Hemolysis | 0.01 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Hepatic Dysfunction | 0.03 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Psychiatric Episode | 0.08 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Hypertension | 0.07 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Venous Thromboembolism | 0.04 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Major Infection | 0.82 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Renal Dysfunction | 0.11 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Myocardial Infarction | 0.01 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Stroke | 0.08 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Suspected Device Thrombosis | 0.01 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Hemorrhagic Stroke | 0.03 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Respiratory Failure | 0.19 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Ischemic Stroke | 0.04 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Adverse Event Rates | Right Heart Failure | 0.27 events per patient year |
Secondary
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.
Time frame: Baseline to 24 months
Population: Analysis population only includes patients still ongoing on LVAD support at the specified time periods who completed the assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HeartMate II (Intent-to-Treat) | EuroQoL 5D-5L (EQ-5D-5L) Total Score | Baseline | 11.2 score on a scale | Standard Deviation 4.4 |
| HeartMate II (Intent-to-Treat) | EuroQoL 5D-5L (EQ-5D-5L) Total Score | 6 months | 8.5 score on a scale | Standard Deviation 3.2 |
| HeartMate II (Intent-to-Treat) | EuroQoL 5D-5L (EQ-5D-5L) Total Score | 24 months | 9.2 score on a scale | Standard Deviation 3.8 |
| HeartMate 3 (Intent-to-Treat) | EuroQoL 5D-5L (EQ-5D-5L) Total Score | Baseline | 11.1 score on a scale | Standard Deviation 4.3 |
| HeartMate 3 (Intent-to-Treat) | EuroQoL 5D-5L (EQ-5D-5L) Total Score | 6 months | 8.5 score on a scale | Standard Deviation 3.3 |
| HeartMate 3 (Intent-to-Treat) | EuroQoL 5D-5L (EQ-5D-5L) Total Score | 24 months | 8.8 score on a scale | Standard Deviation 3.6 |
Secondary
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.
Time frame: Baseline to 24 months
Population: Analysis population only includes patients still ongoing on LVAD support at the specified time periods who completed the assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HeartMate II (Intent-to-Treat) | EuroQol-5D-5L Visual Analogue Scale | Baselline | 48 score on a scale | Standard Deviation 25 |
| HeartMate II (Intent-to-Treat) | EuroQol-5D-5L Visual Analogue Scale | 6 months | 74 score on a scale | Standard Deviation 19 |
| HeartMate II (Intent-to-Treat) | EuroQol-5D-5L Visual Analogue Scale | 24 months | 75 score on a scale | Standard Deviation 19 |
| HeartMate 3 (Intent-to-Treat) | EuroQol-5D-5L Visual Analogue Scale | Baselline | 50 score on a scale | Standard Deviation 24 |
| HeartMate 3 (Intent-to-Treat) | EuroQol-5D-5L Visual Analogue Scale | 6 months | 76 score on a scale | Standard Deviation 18 |
| HeartMate 3 (Intent-to-Treat) | EuroQol-5D-5L Visual Analogue Scale | 24 months | 76 score on a scale | Standard Deviation 19 |
Secondary
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.
Time frame: Baseline to 24 months
Population: Analysis population only includes patients still ongoing on LVAD support at the specified time periods who completed the assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HeartMate II (Intent-to-Treat) | Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | Baseline | 40 score on a scale | Standard Deviation 23 |
| HeartMate II (Intent-to-Treat) | Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | 6 months | 70 score on a scale | Standard Deviation 21 |
| HeartMate II (Intent-to-Treat) | Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | 24 months | 68 score on a scale | Standard Deviation 23 |
| HeartMate 3 (Intent-to-Treat) | Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | Baseline | 39 score on a scale | Standard Deviation 20 |
| HeartMate 3 (Intent-to-Treat) | Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | 6 months | 70 score on a scale | Standard Deviation 20 |
| HeartMate 3 (Intent-to-Treat) | Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | 24 months | 69 score on a scale | Standard Deviation 22 |
Secondary
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.
Time frame: Baseline to 24 months
Population: Analysis population only includes patients still ongoing on LVAD support at the specified time periods who completed the assessment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HeartMate II (Intent-to-Treat) | New York Heart Association (NYHA) Classification | Class I or II at Baseline | 0 Participants |
| HeartMate II (Intent-to-Treat) | New York Heart Association (NYHA) Classification | Class I or II at 6 Months | 310 Participants |
| HeartMate II (Intent-to-Treat) | New York Heart Association (NYHA) Classification | Class I or II at 24 Months | 176 Participants |
| HeartMate 3 (Intent-to-Treat) | New York Heart Association (NYHA) Classification | Class I or II at Baseline | 0 Participants |
| HeartMate 3 (Intent-to-Treat) | New York Heart Association (NYHA) Classification | Class I or II at 6 Months | 340 Participants |
| HeartMate 3 (Intent-to-Treat) | New York Heart Association (NYHA) Classification | Class I or II at 24 Months | 219 Participants |
Secondary
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.
Time frame: As they occur up to 24 months or to Outcome, whichever occurs first
Population: All subjects who underwent implant with the assigned device
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HeartMate II (Intent-to-Treat) | Powered Secondary End Point: Pump Replacement at Two Years | 57 Participants |
| HeartMate 3 (Intent-to-Treat) | Powered Secondary End Point: Pump Replacement at Two Years | 12 Participants |
Comparison: Based on data in the Sponsor's device tracking database, 7% of patients with the HeartMate II LVAS receive a pump replacement by 24 months. The expected proportion of patients with the HeartMate 3 LVAS to receive a pump replacement by 24 months was assumed to be 3%. We estimated that to demonstrate superiority of HeartMate 3 to HeartMate II with a power of 80% and α = 0.05 (2-sided), a total of 1028 patients (514 per arm) were required using the Fisher's exact test.p-value: <0.00195% CI: [0.11, 0.38]Fisher Exact
Secondary
Rehospitalizations
Rate of all cause rehospitalization
Time frame: From initial discharge to two years post-implant
Population: Analysis population only includes Subjects who were discharged on LVAD support from the implant hospitalization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HeartMate II (Intent-to-Treat) | Rehospitalizations | 2.47 events per patient year |
| HeartMate 3 (Intent-to-Treat) | Rehospitalizations | 2.26 events per patient year |
Secondary
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.
Time frame: Baseline to 24 months
Population: Analysis population only includes patients still ongoing on LVAD support at the specified time periods who completed the assessment. Patients unable to walk due to heart failure symptoms were assigned a distance of zero.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HeartMate II (Intent-to-Treat) | Six Minute Walk Test | Baseline | 129 meters | Standard Deviation 156 |
| HeartMate II (Intent-to-Treat) | Six Minute Walk Test | 6 months | 327 meters | Standard Deviation 136 |
| HeartMate II (Intent-to-Treat) | Six Minute Walk Test | 24 months | 361 meters | Standard Deviation 337 |
| HeartMate 3 (Intent-to-Treat) | Six Minute Walk Test | Baseline | 136 meters | Standard Deviation 160 |
| HeartMate 3 (Intent-to-Treat) | Six Minute Walk Test | 6 months | 310 meters | Standard Deviation 142 |
| HeartMate 3 (Intent-to-Treat) | Six Minute Walk Test | 24 months | 323 meters | Standard Deviation 156 |