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

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 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.

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