Trial Outcomes & Findings for Prevention of Non-Surgical Bleeding by Management of HeartMate II Patients Without Antiplatelet Therapy (NCT NCT02836652)

Last Updated: 2022-06-27

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

72 participants

Primary outcome timeframe

6 months post initial implantation

Results posted on

2022-06-27

Participant Flow

Participant milestones

Participant milestones
Measure	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)	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)
Overall Study STARTED	35	37
Overall Study As-treated Population	31	34
Overall Study COMPLETED	17	18
Overall Study NOT COMPLETED	18	19

Reasons for withdrawal

Reasons for withdrawal
Measure	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)	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)
Overall Study Death	3	3
Overall Study Transplant/Explant	3	4
Overall Study Withdrawn	9	9
Overall Study Not on treatment regimen post-op day 15	3	3

Baseline Characteristics

Prevention of Non-Surgical Bleeding by Management of HeartMate II Patients Without Antiplatelet Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=31 Participants 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)	Aspirin n=34 Participants 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)	Total n=65 Participants Total of all reporting groups
Age, Continuous	68.2 years STANDARD_DEVIATION 5.9 • n=5 Participants	65.6 years STANDARD_DEVIATION 6.5 • n=7 Participants	66.8 years STANDARD_DEVIATION 6.3 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	31 Participants n=7 Participants	56 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants	24 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	35 participants n=5 Participants	37 participants n=7 Participants	72 participants n=5 Participants
Ischemic Heart Failure	15 Participants n=5 Participants	24 Participants n=7 Participants	39 Participants n=5 Participants
History of Atrial Fibrillation	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
History of Stroke	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
History of Bleed	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
History of Gastrointestinal Bleed	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
History of Myocardial Infarction	12 Participants n=5 Participants	21 Participants n=7 Participants	33 Participants n=5 Participants
History of Diabetes	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
History of Aortic Stenosis	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
History of Carotid Artery Disease	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Left Ventricular Ejection Fraction (%) - mean ± standard deviation (SD)	18.0 % STANDARD_DEVIATION 5.9 • n=5 Participants	16.8 % STANDARD_DEVIATION 5.1 • n=7 Participants	17.4 % STANDARD_DEVIATION 5.5 • n=5 Participants
Right Atrial Pressure (mm-Hg) - mean ± SD	10.5 mm-Hg STANDARD_DEVIATION 7.0 • n=5 Participants	9.6 mm-Hg STANDARD_DEVIATION 5.5 • n=7 Participants	10.0 mm-Hg STANDARD_DEVIATION 6.2 • n=5 Participants
Mean Arterial Pressure (mm-Hg) - mean ± SD	83.8 mm-Hg STANDARD_DEVIATION 10.3 • n=5 Participants	85.6 mm-Hg STANDARD_DEVIATION 14.2 • n=7 Participants	84.8 mm-Hg STANDARD_DEVIATION 12.4 • n=5 Participants
Estimated Glomerular Filtration Rate	56.2 ml/min/1.73 m^2 STANDARD_DEVIATION 17.3 • n=5 Participants	58.6 ml/min/1.73 m^2 STANDARD_DEVIATION 22.0 • n=7 Participants	57.5 ml/min/1.73 m^2 STANDARD_DEVIATION 19.8 • n=5 Participants
Destination Therapy	28 Participants n=5 Participants	29 Participants n=7 Participants	57 Participants n=5 Participants
Inter-agency Registry for Mechanically Assisted Circulatory Support (INTERMACS) <= 3	28 Participants n=5 Participants	26 Participants n=7 Participants	54 Participants n=5 Participants
Cardiac Re-synchronization Therapy with Defibrillator	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months post initial implantation

Population: As-treated population

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants 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)	Aspirin n=34 Participants 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)
Safety Endpoint: % of Patients With Non-surgical Bleeding at 6 Months Post HeartMate II Implant	12 Participants	15 Participants

PRIMARY outcome

Timeframe: 6 months post initial implantation

Population: As-treated population

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.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants 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)	Aspirin n=34 Participants 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)
Efficacy Endpoint: % of Patients With Thromboembolic Events at 6 Months Post HeartMate II Implant	4 Participants	3 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months post-implant

Rates of bleeding, gastrointestinal (GI) bleeding, suspected and confirmed pump thrombosis, stroke, hemolysis, anticoagulation, survival.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants 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)	Aspirin n=34 Participants 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)
Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant Confirmed Pump Thrombosis	6.5 percentage of subjects	5.9 percentage of subjects
Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant Major Bleeding	38.7 percentage of subjects	64.7 percentage of subjects
Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant GI Bleeding	25.8 percentage of subjects	29.4 percentage of subjects
Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant Ischemic Stroke	12.9 percentage of subjects	14.7 percentage of subjects
Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant Hemorrhagic Stroke	6.5 percentage of subjects	5.9 percentage of subjects
Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant Transient Ischemic Attack	9.7 percentage of subjects	0 percentage of subjects
Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant Hemolysis	22.6 percentage of subjects	17.6 percentage of subjects
Descriptive Endpoint: Percent of Patients With Adverse Events at 1-year Post HeartMate II Implant Suspected Pump Thrombosis	9.7 percentage of subjects	8.8 percentage of subjects

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months post-implant

Population: As-treated population

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.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants 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)	Aspirin n=34 Participants 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)
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	100 percentage of subjects
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	100 percentage of subjects
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	100 percentage of subjects
Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices Was the pump anchored?	76.7 percentage of subjects	85.3 percentage of subjects
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	100 percentage of subjects
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	52.9 percentage of subjects
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	100 percentage of subjects
Adherence to Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) Study Recommended Practices Was Heparin Bridging started?	76.7 percentage of subjects	85.3 percentage of subjects
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	50.0 percentage of subjects
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	26.5 percentage of subjects
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	73.5 percentage of subjects
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	41.2 percentage of subjects
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	9.4 percentage of subjects

Adverse Events

Placebo

Serious events: 21 serious events

Other events: 0 other events

Deaths: 3 deaths

Aspirin

Serious events: 26 serious events

Other events: 0 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=31 participants at risk 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)	Aspirin n=34 participants at risk 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)
Vascular disorders Major Bleeding	38.7% 12/31 • Number of events 20 • At the end of study follow-up: 12-months HM II implant. Adverse events and deaths occurring in the "as-treated population" are reported here. This includes patients that consented to participate in the study and were able to start the research drug within 15 days of HM II implant.	64.7% 22/34 • Number of events 35 • At the end of study follow-up: 12-months HM II implant. Adverse events and deaths occurring in the "as-treated population" are reported here. This includes patients that consented to participate in the study and were able to start the research drug within 15 days of HM II implant.
Nervous system disorders Stroke	19.4% 6/31 • Number of events 6 • At the end of study follow-up: 12-months HM II implant. Adverse events and deaths occurring in the "as-treated population" are reported here. This includes patients that consented to participate in the study and were able to start the research drug within 15 days of HM II implant.	20.6% 7/34 • Number of events 7 • At the end of study follow-up: 12-months HM II implant. Adverse events and deaths occurring in the "as-treated population" are reported here. This includes patients that consented to participate in the study and were able to start the research drug within 15 days of HM II implant.
Blood and lymphatic system disorders Hemolysis	22.6% 7/31 • Number of events 7 • At the end of study follow-up: 12-months HM II implant. Adverse events and deaths occurring in the "as-treated population" are reported here. This includes patients that consented to participate in the study and were able to start the research drug within 15 days of HM II implant.	17.6% 6/34 • Number of events 6 • At the end of study follow-up: 12-months HM II implant. Adverse events and deaths occurring in the "as-treated population" are reported here. This includes patients that consented to participate in the study and were able to start the research drug within 15 days of HM II implant.
Product Issues Suspected Pump Thrombosis	9.7% 3/31 • Number of events 4 • At the end of study follow-up: 12-months HM II implant. Adverse events and deaths occurring in the "as-treated population" are reported here. This includes patients that consented to participate in the study and were able to start the research drug within 15 days of HM II implant.	8.8% 3/34 • Number of events 3 • At the end of study follow-up: 12-months HM II implant. Adverse events and deaths occurring in the "as-treated population" are reported here. This includes patients that consented to participate in the study and were able to start the research drug within 15 days of HM II implant.

Other adverse events

Adverse event data not reported

Additional Information

Poornima Sood

Abbott

Phone: 7818528334

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place