Cardiomyopathies, Heart Failure, Congestive, Ventricular Dysfunction
Conditions
Keywords
Heart-assist devices
Brief summary
The purpose of this study is to determine the safety and effectiveness of the Thoratec HeartMate II Left Ventricular Assist System (LVAS) as a bridge to cardiac transplantation in end-stage heart failure patients who are listed for cardiac transplant but are at imminent risk of dying. The HeartMate II LVAS was approved by the US FDA on April 21, 2008, as a bridge to cardiac transplantation (reference PMA P060040). It was approved for commercial distribution in Canada on May 20, 2009 (reference Medical Device Licence #79765). Patients enrolled into the clinical trial will continue to be followed until all have reached a clinical outcome.
Detailed description
The HeartMate II is a high speed, electric, axial flow, rotary blood pump. The pump drains blood from the left ventricular apex via a rigid inlet cannula and ejects into the aortic root via an outflow cannula joined to the aorta with an end to side anastomosis. Power and control of the pump are delivered through a percutaneous cable from the pump to the belt-worn System Driver. Patient outcomes will be compared to objective performance criteria based on historical data from other Thoratec implantable ventricular assist devices.
Interventions
DEVICEThoratec HeartMate II Left Ventricular Assist System (LVAS)
Implantation of ventricular assist device to provide hemodynamic support
Sponsors
Thoratec Corporation
Abbott Medical Devices
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
The following are general criteria; more specific conditions are included in the study protocol: * Listed for cardiac transplantation * NYHA Class IV heart failure symptoms * On inotropic support, if tolerated * Despite medical therapy, the patient must meet hemodynamic criteria for cardiogenic shock
Exclusion criteria
The following are general criteria; more specific conditions are included in the study protocol: * Evidence of, or risk factors for end-organ dysfunction that would make LVAS implantation futile * Existence of factors that would adversely affect patient survival or function of the LVAS. * Intolerance to anticoagulant or antiplatelet therapies. * Existence of any ongoing mechanical circulatory support other than intra-aortic balloon counterpulsation. * Participation in any other clinical investigation that is likely to confound study results or affect study outcome.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival | 180 days | Survival to cardiac transplantation or 180 days on left ventricular assist system (LVAS) support while remaining listed for cardiac transplantation as United Network for Organ Sharing (UNOS)status 1A or 1B (please refer to www.unos.org for complete definitions of status). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kansas City Cardiomyopathy Questionaire (KCCQ) | baseline to 6 months | KCCQ is a validated instrument to self assess quality of life including physical function and social function. The instrument provides two scores, the Overall Summary (OSS) and Clinical Summary (CSS). Scores are calculated based on responses to the questionnaire, on a scale from 0-100. The higher the score, the better the quality of life. The patients' scores at six months were compared to their baseline scores and the resulting positive scores indicated improved quality of life. |
| New York Heart Association (NYHA) Classification | baseline, 1 month, 3 months, 6 months | NYHA 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 |
| Minnesota Living With Heart Failure Questionnaire (MLWHF) | Baseline to 6 months | MLWHF is a validated instrument to self assess how heart failure and its treatment affect the key physical, emotional, social and psychological dimensions of quality of life. The instrument is made up of 21 items that assess the patient's perception of these dimensions on a scale ranging from no (0) to very much (5). The total MLWHF score is calculated by adding the scores for all 21 items (range, 0-105). A lower score indicates a better quality of life. The patients' score at six months was compared to their baseline score and the resulting negative score indicates improved quality of life. |
| Clinical Reliability (Malfunctions/Failures) | continuous | Confirmed malfunctions/Serious Adverse Events |
| Reoperations | continuous | Additional surgery after the initial implant operation |
| Post-transplant Survival | 30 days, 1 year | 30 day and 1 year post transplant survival |
| Six Minute Walk Test (6MWT) | baseline to 6 months | 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. |
Countries
Canada, United States
Participant flow
Recruitment details
486 patients were recruited at 36 cardiac transplantation hospitals between 8 Mar 2005 and 21 Apr 2008. After enrolling the initial 133 patients prespecified by the study protocol, an additional 353 patients were enrolled under a Continued Access Protocol(CAP) and in a concurrent Canadian study.
Pre-assignment details
194 patients were followed to at least 1 year after implantation of the device, all 133 of the Pivotal Study Cohort patients and 61 of the US CAP patients, results of which are summarized below and in the final FDA-approved labeling for the HeartMate II LVAS. The remaining 292 patients followed for less than 1 year are not included.
Participants by arm
| Arm | Count |
|---|---|
| HM II HeartMate II LVAS used as a bridge to cardiac transplantation with at least 1-year follow-up (133 Pivotal Study Cohort and 61 US Continued Access Protocol) | 194 |
| Total | 194 |
Baseline characteristics
| Characteristic | HM II |
|---|---|
| Age, Continuous | 50.6 years STANDARD_DEVIATION 13 |
| Body Surface Area | 1.99 sq. meter STANDARD_DEVIATION 0.29 |
| Cardiac Index | 2.0 L/min/m^2 STANDARD_DEVIATION 0.5 |
| PCWP | 26.0 mmHg STANDARD_DEVIATION 7.7 |
| Sex: Female, Male Female | 44 Participants |
| Sex: Female, Male Male | 150 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 194 |
| serious Total, serious adverse events | 194 / 194 |
Outcome results
Primary
Survival
Survival to cardiac transplantation or 180 days on left ventricular assist system (LVAS) support while remaining listed for cardiac transplantation as United Network for Organ Sharing (UNOS)status 1A or 1B (please refer to www.unos.org for complete definitions of status).
Time frame: 180 days
Population: The first consecutive 194 patients enrolled under the Pivotal Study Protocol (n=133) and the Continued Access Protocol (CAP, n=61) were analyzed when the last subject reached the 1 year followup point on September 14, 2007. Analysis was Intent To Treat (ITT).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HM II | Survival | Transplanted | 112 participants |
| HM II | Survival | Myocardial recovery, device removed | 6 participants |
| HM II | Survival | Alive on device at 180 days & UNOS Status 1A or 1B | 18 participants |
| HM II | Survival | Alive on device at 180 days, not Status 1A or 1B | 19 participants |
| HM II | Survival | Received other ventricular assist device | 3 participants |
| HM II | Survival | Expired prior to 180 days while on VAD support | 36 participants |
Secondary
Clinical Reliability (Malfunctions/Failures)
Confirmed malfunctions/Serious Adverse Events
Time frame: continuous
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HM II | Clinical Reliability (Malfunctions/Failures) | Pump | 7 Number of Serious Events |
| HM II | Clinical Reliability (Malfunctions/Failures) | Inflow Cannula | 2 Number of Serious Events |
| HM II | Clinical Reliability (Malfunctions/Failures) | Outflow Cannula | 2 Number of Serious Events |
| HM II | Clinical Reliability (Malfunctions/Failures) | System Controller | 10 Number of Serious Events |
| HM II | Clinical Reliability (Malfunctions/Failures) | System Monitor | 0 Number of Serious Events |
| HM II | Clinical Reliability (Malfunctions/Failures) | Display Module | 0 Number of Serious Events |
| HM II | Clinical Reliability (Malfunctions/Failures) | Power Base Unit | 0 Number of Serious Events |
| HM II | Clinical Reliability (Malfunctions/Failures) | Power Base Unit Cable | 1 Number of Serious Events |
| HM II | Clinical Reliability (Malfunctions/Failures) | Batteries | 1 Number of Serious Events |
| HM II | Clinical Reliability (Malfunctions/Failures) | Battery Clips | 0 Number of Serious Events |
| HM II | Clinical Reliability (Malfunctions/Failures) | Shower Kit | 0 Number of Serious Events |
| HM II | Clinical Reliability (Malfunctions/Failures) | Surgical Accessories | 0 Number of Serious Events |
Secondary
Kansas City Cardiomyopathy Questionaire (KCCQ)
KCCQ is a validated instrument to self assess quality of life including physical function and social function. The instrument provides two scores, the Overall Summary (OSS) and Clinical Summary (CSS). Scores are calculated based on responses to the questionnaire, on a scale from 0-100. The higher the score, the better the quality of life. The patients' scores at six months were compared to their baseline scores and the resulting positive scores indicated improved quality of life.
Time frame: baseline to 6 months
Population: Patients alive and capable of performing the test at 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HM II | Kansas City Cardiomyopathy Questionaire (KCCQ) | KCCQ Overall Summary Score (OSS) | 29.5 Units on a KCCQ Score scale | Standard Error 2.7 |
| HM II | Kansas City Cardiomyopathy Questionaire (KCCQ) | KCCQ Clinical Summary Score (CSS) | 28.8 Units on a KCCQ Score scale | Standard Error 2.4 |
Secondary
Minnesota Living With Heart Failure Questionnaire (MLWHF)
MLWHF is a validated instrument to self assess how heart failure and its treatment affect the key physical, emotional, social and psychological dimensions of quality of life. The instrument is made up of 21 items that assess the patient's perception of these dimensions on a scale ranging from no (0) to very much (5). The total MLWHF score is calculated by adding the scores for all 21 items (range, 0-105). A lower score indicates a better quality of life. The patients' score at six months was compared to their baseline score and the resulting negative score indicates improved quality of life.
Time frame: Baseline to 6 months
Population: Patients alive and capable of performing the test at 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HM II | Minnesota Living With Heart Failure Questionnaire (MLWHF) | -32.3 units on a MLWHF Score scale | Standard Error 2.9 |
Secondary
New York Heart Association (NYHA) Classification
NYHA 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, 1 month, 3 months, 6 months
Population: All patients who survived to interval are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HM II | New York Heart Association (NYHA) Classification | Baseline NYHA Class | 4.0 units on NYHA scale | Full Range 0.1 |
| HM II | New York Heart Association (NYHA) Classification | Month 1 NYHA Class | 2.2 units on NYHA scale | Full Range 0.8 |
| HM II | New York Heart Association (NYHA) Classification | Month 3 NYHA Class | 1.8 units on NYHA scale | Full Range 0.7 |
| HM II | New York Heart Association (NYHA) Classification | Month 6 NYHA Class | 1.7 units on NYHA scale | Full Range 0.7 |
Secondary
Post-transplant Survival
30 day and 1 year post transplant survival
Time frame: 30 days, 1 year
Population: Patients (n=112) who recieved a cardiac transplant were followed at 30 day and 1 year post-transplant to determine if the device influenced post-transplant survival.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HM II | Post-transplant Survival | Survival at 30 days (%) | 96 percentage of participants |
| HM II | Post-transplant Survival | Survival at 1 year (%) | 87 percentage of participants |
Secondary
Reoperations
Additional surgery after the initial implant operation
Time frame: continuous
Population: The first consecutive 194 patients enrolled under the Pivotal Study Protocol (n=133) and the Continued Access Protocol (CAP, n=61) were analyzed when the last subject reached the 1 year followup point on September 14, 2007. Analysis was Intent To Treat (ITT).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HM II | Reoperations | HMII Replacement | 8 Number of Events |
| HM II | Reoperations | Bleeding | 104 Number of Events |
| HM II | Reoperations | Mediastinal exploration, evacuation and chest clos | 7 Number of Events |
| HM II | Reoperations | Chest closure or reinforcement of closure | 32 Number of Events |
| HM II | Reoperations | ICD placement or exchange | 8 Number of Events |
| HM II | Reoperations | Evacuation of pericardial effusion | 1 Number of Events |
| HM II | Reoperations | RVAD placemant or removal | 9 Number of Events |
| HM II | Reoperations | Tracheostomy | 9 Number of Events |
| HM II | Reoperations | Cholecystectomy, feeding tube placement, tracheost | 1 Number of Events |
| HM II | Reoperations | Evacuation of pleural effusion, dialysis catheter | 1 Number of Events |
| HM II | Reoperations | Feeding tube placement, chest tube placement | 1 Number of Events |
| HM II | Reoperations | Left lower lobe wedge resection | 1 Number of Events |
| HM II | Reoperations | LVAD evaluation and repair | 2 Number of Events |
| HM II | Reoperations | Mediastinal exploration and evacuation | 1 Number of Events |
| HM II | Reoperations | Total abdominal cholectomy with end-ileostomy | 1 Number of Events |
| HM II | Reoperations | Device explant | 1 Number of Events |
| HM II | Reoperations | Feeding tube placement | 1 Number of Events |
| HM II | Reoperations | Mediastinal exploration, chest closure, gortex gra | 2 Number of Events |
| HM II | Reoperations | Mediastinal exploration , evacuation, pacemaker re | 1 Number of Events |
| HM II | Reoperations | Pericardial window | 1 Number of Events |
| HM II | Reoperations | Mediastinal exploration , wound debridement, ICD r | 1 Number of Events |
| HM II | Reoperations | Placement of chest tubes | 1 Number of Events |
| HM II | Reoperations | Removal of foreign body | 1 Number of Events |
Secondary
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 to 6 months
Population: Mean change from baseline in 6MWT distance at Month 1, 3, and 6. Only patients alive, capable and willing to perform test are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HM II | Six Minute Walk Test (6MWT) | Month 3 (N = 101) | 235.4 meters | Standard Error 22 |
| HM II | Six Minute Walk Test (6MWT) | Month 6 (N = 64) | 296.8 meters | Standard Error 27.8 |
| HM II | Six Minute Walk Test (6MWT) | Month 1 (N = 151) | 149.2 meters | Standard Error 14.5 |