Overview
Heart failure is a world epidemic. LVADs are increasingly used as they have demonstrated improved survival rates compared to optimal medical management. Improving outcomes have been seen with the newer LVAD technology, the HeartMate 3 (Abbott, Chicago, IL), however, hemocompatibility related adverse events, including thrombosis and bleeding, are still a major cause of morbidity and mortality. The recent ARIES trial showed that in patients with advanced heart failure treated with a HeartMate3 LVAD, avoidance of aspirin as part of an antithrombotic regimen, which includes vitamin K antagonist (VKA), is not inferior to a regimen containing aspirin, does not increase thromboembolism risk, and is associated with a reduction in bleeding events.
This clinical investigation is a prospective, randomized, controlled study of advanced heart failure patients supports with the HeartMate3 for more then 3 months with two different antithrombotic regimens: VKA with and without aspirin. The objective of this investigation is to study the safety and efficacy of an antithrombotic regimen without antiplatelet therapy.
Description
Objective: To study the safety and efficacy of an anti-platelet-free antithrombotic regimen in patients with advanced heart failure who are chronically supported with the HeartMate 3 LVAD.
Hypothesis: The withdrawal of aspirin from the antithrombotic regimen of HeartMate3 LVAD patients will not adversely affect safety and efficacy and may reduce non-surgical bleeding.
Clinical Investigation Design: This is a prospective, randomized, controlled clinical investigation of advanced heart failure patients who are chronically supported with the HeartMate 3 LVAD. The study will compare two different antithrombotic regimens: VKA with aspirin versus VKA without aspirin.
End points:
Primary end point:
- Composite of Survival free of any major hemocompatibility related adverse event at
1-year post randomization.
- Major Hemocompatibility Related Adverse Event: Stroke, Pump Thrombosis (suspected or confirmed), major non surgical Bleeding (moderate or severe) (including intracranial bleeds that do not meet the stroke definition), Arterial Peripheral Thromboembolism
Secondary end point:
- Non-surgical Major Hemorrhagic Events
- Non-surgical Major Thrombotic Events
- Survival
- Stroke Rates
- Pump Thrombosis Rates
- Bleeding Rates, including:
- Non-surgical Bleeding
- Moderate Bleeding
- Severe Bleeding
- Fatal Bleeding
- GI Bleeding Descriptive endpoints
- Hemocompatibility score:
a tiered hierarchal score that weighs each hemocompatibility related adverse event by its escalating clinical relevanceāø
- Rehospitalizations
- Economic Cost Implications
- Subgroup analysis (patients with increased bleeding/thrombotic risk (i.e prior HRAE events)
Number of Subjects Required for Inclusion in Clinical Investigation:
Based on ARIES results, 58 patients will need to be enrolled in each arm (116 total) to achieve 80% power to prove that the non-aspirin group is non-inferior to the aspirin group using a non-inferiority margin of 15% with the Farrington-Manning risk difference approach to non-inferiority at a one-sided alpha = 0.05. To account for an expected 10% dropout rate, up to 128 patients will be randomized in the trial.
Eligibility
Inclusion Criteria:
- Participant will have HeartMate3 LVAD implanted > 3 months before enrollment.
- >18 years old
- Treated with aspirin and VKA
- Participant must provide written informed consent prior to any clinical investigation-related procedure
Exclusion Criteria:
- Investigator-mandated antiplatelet therapy for other conditions (including mandated presence or absence of antiplatelet agent)
- Participation in any other clinical investigation(s) involving an MCS device, or interventional investigation(s) likely to confound study results or affect study outcome
- Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results
- Pregnant and on appropriate contraception