Advanced Refractory Left Ventricular Heart Failure
Conditions
Keywords
Heart Failure, Ventricular Dysfunction, Cardiomyopathies, Heart Disease, Cardiovascular Disease, Heart-assist devices, Thoratec Corporation
Brief summary
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).
Interventions
Implantation of left ventricular assist device for hemodynamic support
Sponsors
Center for Life Sciences
Emergo
KCRI
Thoratec Corporation
Abbott Medical Devices
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival | 6 months | Comparison of survival at 6 months of Left Ventricular Assist Device (LVAD) support to a performance goal established using matched HeartMate II INTERMACS data |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional Status - Six Minute Walk Test (6MWT) | Baseline, Month 1, Month 3, Month 6 | 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. |
| Functional Status - New York Heart Association (NYHA) Classification | Baseline, Month 1, Month 3, Month 6 | 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 |
| All Adverse Events | As they occurred, Baseline through 180 Days | Frequency of pre-defined anticipated adverse events |
| Quality of Life (EQ-5D-5L) | Baseline, Month 1, Month 3, Month 6 | 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. |
| Reoperations | As they occurred, Baseline through 180 Days | Frequency of reoperations |
| Rehospitalizations | As they occurred, Baseline through 180 Days | Frequency and incidence of rehospitalizations |
| Stroke Free Survival | 6 months | Percentage of participants free of debilitating stroke (Modified Rankin Score \> 3) |
| Device Malfunctions | 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 | Frequency and incidence of device malfunction |
Countries
Australia, Austria, Canada, Czechia, Germany, Kazakhstan
Participant flow
Recruitment details
50 patients were recruited at 10 cardiac transplant centers and implanted between June 25, 2014, and November 27, 2014
Pre-assignment details
The data presented in this record includes all 50 patients followed through to the 6-month primary endpoint.
Participants by arm
| Arm | Count |
|---|---|
| HeartMate 3 HeartMate 3 Left Ventricular Assist System (HM3 LVAS) used for advanced refractory left ventricular heart failure (50 Subjects in the Study Cohort). | 50 |
| Total | 50 |
Baseline characteristics
| Characteristic | HeartMate 3 |
|---|---|
| Age, Continuous | 58.9 Years STANDARD_DEVIATION 13.5 |
| Body Surface Area | 2 M^2 STANDARD_DEVIATION 0.2 |
| Cardiac Index | 1.8 L/min/m^2 STANDARD_DEVIATION 0.5 |
| Region of Enrollment Australia | 1 participants |
| Region of Enrollment Austria | 7 participants |
| Region of Enrollment Canada | 3 participants |
| Region of Enrollment Czech Republic | 10 participants |
| Region of Enrollment Germany | 21 participants |
| Region of Enrollment Kazakhstan | 8 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 50 |
| other Total, other adverse events | 34 / 50 |
| serious Total, serious adverse events | 34 / 50 |
Outcome results
Primary
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
Time frame: 6 months
Population: All 50 patients were analyzed when the last patient reached the 6-month primary endpoint on May 26, 2015
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HeartMate 3 | Survival | 92 Percentage of Participants who Survived |
Secondary
All Adverse Events
Frequency of pre-defined anticipated adverse events
Time frame: As they occurred, Baseline through 180 Days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HeartMate 3 | All Adverse Events | Right heart failure | 10 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Right heart failure w RVAD | 4 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Wound dehiscence | 8 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Other | 54 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Bleeding | 38 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Bleeding requiring surgery | 14 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Gastrointestinal bleeding | 8 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Cardiac Arrhythmia | 34 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Pericardial fluid | 2 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Internal device malfunction | 6 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Pump thrombosis | 0 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | External device malfunctions | 24 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Hemolysis | 0 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Hepatic dysfunction | 2 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Hypertension | 2 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Any infection | 36 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Infection - sepsis | 16 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Infection - driveline | 10 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Myocardial infarction | 0 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Any stroke | 12 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Stroke - ischemic | 8 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Stroke - hemorrhagic | 4 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Neurologic dysfunction | 8 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Psychiatric episode | 6 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Renal dysfunction | 10 % of Participants with Adverse Events |
| HeartMate 3 | All Adverse Events | Respiratory failure | 16 % of Participants with Adverse Events |
Secondary
Device Malfunctions
Frequency and incidence of device malfunction
Time frame: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HeartMate 3 | Device Malfunctions | Pump malfunctions | 0 Number of events |
| HeartMate 3 | Device Malfunctions | Non-pump malfunction: internal component | 3 Number of events |
| HeartMate 3 | Device Malfunctions | Non-pump malfunction: External components | 14 Number of events |
Secondary
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
Time frame: Baseline, Month 1, Month 3, Month 6
Population: Only patients alive, capable and willing to perform test are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HeartMate 3 | Functional Status - New York Heart Association (NYHA) Classification | Baseline NYHA I or II | 0 percentage of participants |
| HeartMate 3 | Functional Status - New York Heart Association (NYHA) Classification | Baseline NYHA III or IV | 100 percentage of participants |
| HeartMate 3 | Functional Status - New York Heart Association (NYHA) Classification | Month 1 NYHA I or II | 64 percentage of participants |
| HeartMate 3 | Functional Status - New York Heart Association (NYHA) Classification | Month 1 NYHA III or IV | 36 percentage of participants |
| HeartMate 3 | Functional Status - New York Heart Association (NYHA) Classification | Month 3 NYHA 1 or II | 81 percentage of participants |
| HeartMate 3 | Functional Status - New York Heart Association (NYHA) Classification | Month 3 NYHA III or IV | 19 percentage of participants |
| HeartMate 3 | Functional Status - New York Heart Association (NYHA) Classification | Month 6 NYHA I or II | 83 percentage of participants |
| HeartMate 3 | Functional Status - New York Heart Association (NYHA) Classification | Month 6 NYHA III or IV | 17 percentage of participants |
Secondary
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.
Time frame: Baseline, Month 1, Month 3, Month 6
Population: Only patients alive, capable and willing to perform test are included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| HeartMate 3 | Functional Status - Six Minute Walk Test (6MWT) | Baseline | 236 meters |
| HeartMate 3 | Functional Status - Six Minute Walk Test (6MWT) | Month 1 | 260 meters |
| HeartMate 3 | Functional Status - Six Minute Walk Test (6MWT) | Month 3 | 375 meters |
| HeartMate 3 | Functional Status - Six Minute Walk Test (6MWT) | Month 6 | 385 meters |
Secondary
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.
Time frame: Baseline, Month 1, Month 3, Month 6
Population: Patients alive and capable of performing the test at 6 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| HeartMate 3 | Quality of Life (EQ-5D-5L) | Baseline | 50 Units on a EQ-5D-5L Score scale |
| HeartMate 3 | Quality of Life (EQ-5D-5L) | Month 1 | 60 Units on a EQ-5D-5L Score scale |
| HeartMate 3 | Quality of Life (EQ-5D-5L) | Month 3 | 70 Units on a EQ-5D-5L Score scale |
| HeartMate 3 | Quality of Life (EQ-5D-5L) | Month 6 | 75 Units on a EQ-5D-5L Score scale |
Secondary
Rehospitalizations
Frequency and incidence of rehospitalizations
Time frame: As they occurred, Baseline through 180 Days
Population: Number of Participants with Rehospitalizations According to Rehospitalization Type
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HeartMate 3 | Rehospitalizations | INR | 5 Participants |
| HeartMate 3 | Rehospitalizations | Suspected device malfunction | 1 Participants |
| HeartMate 3 | Rehospitalizations | Transplant/ Transplant evaluation | 1 Participants |
| HeartMate 3 | Rehospitalizations | Anticoagulation maintenance | 1 Participants |
| HeartMate 3 | Rehospitalizations | Routine testing | 1 Participants |
| HeartMate 3 | Rehospitalizations | ICD therapy | 1 Participants |
| HeartMate 3 | Rehospitalizations | Suspected driveline infection | 1 Participants |
| HeartMate 3 | Rehospitalizations | Bleeding | 4 Participants |
| HeartMate 3 | Rehospitalizations | Infection | 6 Participants |
| HeartMate 3 | Rehospitalizations | Neurologic dysfunction | 1 Participants |
| HeartMate 3 | Rehospitalizations | Arrythmia | 1 Participants |
| HeartMate 3 | Rehospitalizations | Volume issue | 3 Participants |
| HeartMate 3 | Rehospitalizations | Chest pain | 2 Participants |
| HeartMate 3 | Rehospitalizations | Other | 9 Participants |
Secondary
Reoperations
Frequency of reoperations
Time frame: As they occurred, Baseline through 180 Days
Population: Twenty-nine (58%) did not have reoperation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HeartMate 3 | Reoperations | Major bleeding | 11 Number of re-operations by reason |
| HeartMate 3 | Reoperations | Cardiac arrhythmia | 1 Number of re-operations by reason |
| HeartMate 3 | Reoperations | Pericardial fluid | 1 Number of re-operations by reason |
| HeartMate 3 | Reoperations | Major infection | 3 Number of re-operations by reason |
| HeartMate 3 | Reoperations | Respiratory failure | 4 Number of re-operations by reason |
| HeartMate 3 | Reoperations | Right heart failure | 3 Number of re-operations by reason |
| HeartMate 3 | Reoperations | Wound dehiscence | 15 Number of re-operations by reason |
| HeartMate 3 | Reoperations | Other | 23 Number of re-operations by reason |
Secondary
Stroke Free Survival
Percentage of participants free of debilitating stroke (Modified Rankin Score \> 3)
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HeartMate 3 | Stroke Free Survival | 90 percentage of participants |