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

NCT ID: NCT06655376

Last Updated: 2024-10-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-02
• Study Completion Date: 2027-04-01

Brief Summary

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.

Detailed 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.

Conditions

Bleeding; Clot Blood

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Warfarin without Aspirin

Participants will only take Warfarin.

Group Type: EXPERIMENTAL

Warfarin

Intervention Type: DRUG

Warfarin dose will be adjusted per patient for a goal INR 2-3. The individualized daily dose could range anywhere from 0.5-2 mg to 5-7 mg. Oral.

Warfarin and Aspirin

This is the control arm. Participants will take Warfarin and aspirin, which is the standard of care.

Group Type: ACTIVE_COMPARATOR

Aspirin

Intervention Type: DRUG

81-100 mg, oral

Warfarin

Intervention Type: DRUG

Warfarin dose will be adjusted per patient for a goal INR 2-3. The individualized daily dose could range anywhere from 0.5-2 mg to 5-7 mg. Oral.

Interventions

Aspirin

81-100 mg, oral

Intervention Type: DRUG

Warfarin

Warfarin dose will be adjusted per patient for a goal INR 2-3. The individualized daily dose could range anywhere from 0.5-2 mg to 5-7 mg. Oral.

Intervention Type: DRUG

Other Intervention Names

ASPIRIN® tablets; Vitamin K antagonist; COUMADIN

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Nir Uriel

Professor of Cardiology (in Medicine)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nir Uriel, MD

Role: PRINCIPAL_INVESTIGATOR

Seymour, Paul, and Gloria Milstein Professor of Cardiology at Columbia University

Locations

Columbia Irving Medical Center

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Boaz Elad, MD

Role: CONTACT

be2335@cumc.columbia.edu

2123057600

Facility Contacts

Boaz Elad, MD

Role: primary

be2335@cumc.columbia.edu

2123057600

Boaz Elad, MD

Role: backup

Nir Uriel, MD

Role: backup

Other Identifiers

AAAV3358

Identifier Type: -

Identifier Source: org_study_id