Heart Failure
Conditions
Keywords
HeartMate II (HMII), Left Ventricular Assist Device (LVAD)
Brief summary
This study is a prospective, multi-center, randomized, double-blind placebo-controlled study of subjects receiving the HM II LVAD as per the current FDA approved indications for use.
Detailed description
This is a post-market clinical study of HM II patient management practices to be conducted in the United States. Subjects will be randomized in a 1:1 fashion to the following research drug groups: 1. Treatment Arm: Warfarin (INR target: 2.0-2.5, median: 2.25) + Placebo (1 pill/day) 2. Control Arm: Warfarin (INR target: 2.0-2.5, median: 2.25) + ASA Therapy (81mg/day) The study will investigate if subjects in the Treatment Arm experience a reduced incidence of non-surgical bleeding, without an increased risk of thromboembolic events.
Interventions
DEVICEHeartMate II (HMII)
Left Ventricular Assist Device
DRUGWarfarin
(INR Target 2.0-2.5, median 2.25, per standard of patient care)
DRUGacetylsalicylic acid (ASA) therapy
(81mg/day)
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is receiving the HM II per standard of care (SOC) in accordance with the FDA approved indications for use * Subject is ≥ 50 years of age * Subject is receiving the HM II as their first LVAD * Subject or legally authorized representative (LAR) has signed an informed consent form (ICF).
Exclusion criteria
* Existence of ongoing mechanical circulatory support (MCS) other than intra-aortic balloon pump or Impella® devices * Participation in any other clinical investigation(s) involving an MCS device, or an investigation(s) that is likely to confound study results or affect study outcome * Antiplatelet therapy is mandated for other conditions, in particular: a) recent coronary artery stenting (≤ 6 months), b) carotid artery disease, and c) other conditions where the investigator is not comfortable leaving subjects off-ASA or starting ASA post LVAD implantation. In situations where the investigator is uncertain, the Steering Committee can provide recommendation to the investigator as needed. * Subjects in whom heart transplantation is expected in ≤ 6 months * Subjects with a known ASA allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Endpoint: % of Patients With Non-surgical Bleeding at 6 Months Post HeartMate II Implant | 6 months post initial implantation | Composite incidence of non-surgical bleeding at 6 months post initial implantation, including but not limited to gastrointestinal, genitourinary, epistaxis, subdural hematoma, and primary hemorrhagic stroke (not due to ischemic conversion, or due to the treatment of a hemolysis/suspected thrombosis event). |
| Efficacy Endpoint: % of Patients With Thromboembolic Events at 6 Months Post HeartMate II Implant | 6 months post initial implantation | Composite incidence of pump thrombosis and thromboembolic stroke at 6 months post initial implantation, including ischemic stroke, or hemorrhagic stroke due to an ischemic conversion/treatment of hemolysis/pump thrombosis event. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | 12 months post-implant | Rates of bleeding, gastrointestinal (GI) bleeding, suspected and confirmed pump thrombosis, stroke, hemolysis, anticoagulation, survival. |
| Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | 12 months post-implant | The PREVENT recommended practices have three objectives: maximizing flow through the pump, reducing the risk of cannula malposition, and ensuring adequate anticoagulation while on left ventricular device support, with the overall goal of reducing pump thrombosis events. These implant techniques are similar to those in the HeartMate II instructions for use, but with modifications derived from clinical experience. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Warfarin (INR Target 2.0-2.5, median 2.25, per standard of patient care) + placebo (1 pill/day) post HeartMate II implant
HeartMate II (HMII): Left Ventricular Assist Device
Warfarin: (INR Target 2.0-2.5, median 2.25, per standard of patient care) | 31 |
| Aspirin Warfarin (INR Target 2.0-2.5, median 2.25, per standard of patient care) + acetylsalicylic acid (ASA) therapy (81mg/day) post HeartMate II implant
HeartMate II (HMII): Left Ventricular Assist Device
Warfarin: (INR Target 2.0-2.5, median 2.25, per standard of patient care)
acetylsalicylic acid (ASA) therapy: (81mg/day) | 34 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 3 |
| Overall Study | Not on treatment regimen post-op day 15 | 3 | 3 |
| Overall Study | Transplant/Explant | 3 | 4 |
| Overall Study | Withdrawn | 9 | 9 |
Baseline characteristics
| Characteristic | Placebo | Aspirin | Total |
|---|---|---|---|
| Age, Continuous | 68.2 years STANDARD_DEVIATION 5.9 | 65.6 years STANDARD_DEVIATION 6.5 | 66.8 years STANDARD_DEVIATION 6.3 |
| Cardiac Re-synchronization Therapy with Defibrillator | 9 Participants | 12 Participants | 21 Participants |
| Destination Therapy | 28 Participants | 29 Participants | 57 Participants |
| Estimated Glomerular Filtration Rate | 56.2 ml/min/1.73 m^2 STANDARD_DEVIATION 17.3 | 58.6 ml/min/1.73 m^2 STANDARD_DEVIATION 22 | 57.5 ml/min/1.73 m^2 STANDARD_DEVIATION 19.8 |
| History of Aortic Stenosis | 0 Participants | 1 Participants | 1 Participants |
| History of Atrial Fibrillation | 13 Participants | 14 Participants | 27 Participants |
| History of Bleed | 1 Participants | 5 Participants | 6 Participants |
| History of Carotid Artery Disease | 3 Participants | 4 Participants | 7 Participants |
| History of Diabetes | 18 Participants | 18 Participants | 36 Participants |
| History of Gastrointestinal Bleed | 0 Participants | 2 Participants | 2 Participants |
| History of Myocardial Infarction | 12 Participants | 21 Participants | 33 Participants |
| History of Stroke | 6 Participants | 2 Participants | 8 Participants |
| Inter-agency Registry for Mechanically Assisted Circulatory Support (INTERMACS) <= 3 | 28 Participants | 26 Participants | 54 Participants |
| Ischemic Heart Failure | 15 Participants | 24 Participants | 39 Participants |
| Left Ventricular Ejection Fraction (%) - mean ± standard deviation (SD) | 18.0 % STANDARD_DEVIATION 5.9 | 16.8 % STANDARD_DEVIATION 5.1 | 17.4 % STANDARD_DEVIATION 5.5 |
| Mean Arterial Pressure (mm-Hg) - mean ± SD | 83.8 mm-Hg STANDARD_DEVIATION 10.3 | 85.6 mm-Hg STANDARD_DEVIATION 14.2 | 84.8 mm-Hg STANDARD_DEVIATION 12.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 9 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 23 Participants | 24 Participants | 47 Participants |
| Region of Enrollment United States | 35 participants | 37 participants | 72 participants |
| Right Atrial Pressure (mm-Hg) - mean ± SD | 10.5 mm-Hg STANDARD_DEVIATION 7 | 9.6 mm-Hg STANDARD_DEVIATION 5.5 | 10.0 mm-Hg STANDARD_DEVIATION 6.2 |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 25 Participants | 31 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 31 | 3 / 34 |
| other Total, other adverse events | 0 / 31 | 0 / 34 |
| serious Total, serious adverse events | 21 / 31 | 26 / 34 |
Outcome results
Primary
Efficacy Endpoint: % of Patients With Thromboembolic Events at 6 Months Post HeartMate II Implant
Composite incidence of pump thrombosis and thromboembolic stroke at 6 months post initial implantation, including ischemic stroke, or hemorrhagic stroke due to an ischemic conversion/treatment of hemolysis/pump thrombosis event.
Time frame: 6 months post initial implantation
Population: As-treated population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Efficacy Endpoint: % of Patients With Thromboembolic Events at 6 Months Post HeartMate II Implant | 4 Participants |
| Aspirin | Efficacy Endpoint: % of Patients With Thromboembolic Events at 6 Months Post HeartMate II Implant | 3 Participants |
Primary
Safety Endpoint: % of Patients With Non-surgical Bleeding at 6 Months Post HeartMate II Implant
Composite incidence of non-surgical bleeding at 6 months post initial implantation, including but not limited to gastrointestinal, genitourinary, epistaxis, subdural hematoma, and primary hemorrhagic stroke (not due to ischemic conversion, or due to the treatment of a hemolysis/suspected thrombosis event).
Time frame: 6 months post initial implantation
Population: As-treated population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Safety Endpoint: % of Patients With Non-surgical Bleeding at 6 Months Post HeartMate II Implant | 12 Participants |
| Aspirin | Safety Endpoint: % of Patients With Non-surgical Bleeding at 6 Months Post HeartMate II Implant | 15 Participants |
Other Pre-specified
Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices
The PREVENT recommended practices have three objectives: maximizing flow through the pump, reducing the risk of cannula malposition, and ensuring adequate anticoagulation while on left ventricular device support, with the overall goal of reducing pump thrombosis events. These implant techniques are similar to those in the HeartMate II instructions for use, but with modifications derived from clinical experience.
Time frame: 12 months post-implant
Population: As-treated population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was the pump positioned below the diaphragm? | 100 percentage of subjects |
| Placebo | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was Heparin Bridging started? | 76.7 percentage of subjects |
| Placebo | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was inflow cannula parallel to septum and oriented | 100 percentage of subjects |
| Placebo | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was Warfarin initiated within 48 hours post HMII i | 66.7 percentage of subjects |
| Placebo | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was the pump pocket inferiorly deep and lateral? | 100 percentage of subjects |
| Placebo | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was a goal INR of 2.0 - 2.5 achieved in post-op da | 50.0 percentage of subjects |
| Placebo | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Location of core: True Apex | 46.7 percentage of subjects |
| Placebo | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was the treatment drug therapy initiated within 5 | 76.7 percentage of subjects |
| Placebo | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was the pump anchored? | 76.7 percentage of subjects |
| Placebo | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Pump speed <9000 leaving OR? | 45.2 percentage of subjects |
| Placebo | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Does the outflow graft avoid the right ventricle? | 93.3 percentage of subjects |
| Placebo | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Pump speed < 9000 at 30 days? | 14.3 percentage of subjects |
| Placebo | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was the pump pocket adequately sized? | 100 percentage of subjects |
| Aspirin | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Pump speed < 9000 at 30 days? | 9.4 percentage of subjects |
| Aspirin | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was the pump pocket adequately sized? | 100 percentage of subjects |
| Aspirin | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was the pump pocket inferiorly deep and lateral? | 100 percentage of subjects |
| Aspirin | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was the pump positioned below the diaphragm? | 100 percentage of subjects |
| Aspirin | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was the pump anchored? | 85.3 percentage of subjects |
| Aspirin | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was inflow cannula parallel to septum and oriented | 100 percentage of subjects |
| Aspirin | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Location of core: True Apex | 52.9 percentage of subjects |
| Aspirin | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Does the outflow graft avoid the right ventricle? | 100 percentage of subjects |
| Aspirin | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was Heparin Bridging started? | 85.3 percentage of subjects |
| Aspirin | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was Warfarin initiated within 48 hours post HMII i | 50.0 percentage of subjects |
| Aspirin | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was a goal INR of 2.0 - 2.5 achieved in post-op da | 26.5 percentage of subjects |
| Aspirin | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Was the treatment drug therapy initiated within 5 | 73.5 percentage of subjects |
| Aspirin | Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices | Pump speed <9000 leaving OR? | 41.2 percentage of subjects |
Other Pre-specified
Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant
Rates of bleeding, gastrointestinal (GI) bleeding, suspected and confirmed pump thrombosis, stroke, hemolysis, anticoagulation, survival.
Time frame: 12 months post-implant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | Ischemic Stroke | 12.9 percentage of subjects |
| Placebo | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | Hemolysis | 22.6 percentage of subjects |
| Placebo | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | GI Bleeding | 25.8 percentage of subjects |
| Placebo | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | Suspected Pump Thrombosis | 9.7 percentage of subjects |
| Placebo | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | Hemorrhagic Stroke | 6.5 percentage of subjects |
| Placebo | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | Confirmed Pump Thrombosis | 6.5 percentage of subjects |
| Placebo | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | Transient Ischemic Attack | 9.7 percentage of subjects |
| Placebo | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | Major Bleeding | 38.7 percentage of subjects |
| Aspirin | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | Hemorrhagic Stroke | 5.9 percentage of subjects |
| Aspirin | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | Major Bleeding | 64.7 percentage of subjects |
| Aspirin | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | GI Bleeding | 29.4 percentage of subjects |
| Aspirin | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | Ischemic Stroke | 14.7 percentage of subjects |
| Aspirin | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | Transient Ischemic Attack | 0 percentage of subjects |
| Aspirin | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | Hemolysis | 17.6 percentage of subjects |
| Aspirin | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | Suspected Pump Thrombosis | 8.8 percentage of subjects |
| Aspirin | Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant | Confirmed Pump Thrombosis | 5.9 percentage of subjects |