Aspirin and Hemocompatibility Events in Chronic Advanced Heart Failure Patients with Assist Device

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.

1. 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 relevance⁸

* 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.