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

Delayed ARIES: Aspirin and Hemocompatibility Events in Advanced Heart Failure Patients Chronically Supported With a Left Ventricular Assist Device

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.

Study Overview

• Status: Recruiting
• Conditions: Bleeding; Clot Blood
• Intervention / Treatment: Drug: Warfarin; Drug: Aspirin

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.

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Nir Uriel, MD; Phone Number: 2123057600; Email: nu2126@cumc.columbia.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia Irving Medical Center
      • Principal Investigator: Nir Uriel, MD
      • Contact: Nir Uriel, MD; Phone Number: 212-305-7600; Email: nu2126@cumc.columbia.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Warfarin without Aspirin; Participants will only take Warfarin.	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.; Other Names: Vitamin K antagonist; COUMADIN
Active Comparator: Warfarin and Aspirin; This is the control arm. Participants will take Warfarin and aspirin, which is the standard of care.	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.; Other Names: Vitamin K antagonist; COUMADIN; Drug: Aspirin; 81-100 mg, oral; Other Names: ASPIRIN® tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of survival free patients of any major hemocompatibility related adverse events.	A Major Hemocompatibility Related Adverse Event is defined as: 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. The events will be recorded and tallied per patient.	1 year post implant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Non-surgical Major Hemorrhagic Events	The following types of events will be recorded and tallied. MODERATE or severe bleeding as defined in the protocol. SEVERE or overt bleeding plus hemoglobin drop of 3 to < 5 g/dL (provided hemoglobin drop is related to bleed). Any transfusion with overt bleeding. Cardiac tamponade. Bleeding requiring surgical intervention for control (excluding dental, nasal, skin, or hemorrhoid). Hypotension attributable to bleeding.	1 year
Number of Non-surgical Major Thrombotic Events	The following types of events will be recorded and tallied: The Device Thrombosis, Stroke, Arterial non-CNS thromboembolism.	1 year
Survival Rate	Patients who survive at 1 year post implant will be recorded and tallied.	1 year
Stroke Incidence	The following types of events will be recorded and tallied. Ischemic Stroke Hemorrhagic Stroke	1 year
Pump Thrombosis Incidence	pump thrombosis or suspected will be recorded and tallied.	1 year
Bleeding Incidence	Bleeding Rates, including Non-surgical Bleeding, Moderate Bleeding, Severe Bleeding, Fatal Bleeding, GI Bleeding will be recorded and tallied.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Rehospitalizations	number of all hospitalizations at 1 year, including number of HF related hospitalizations, will be tallied.	1 year
Averaged Days of hospitalization	This is to measure economic cost. Health resource utilization will be assessed by comparing days hospitalized (categorized by intensive care vs general ward) between groups.	1 year
Number of patients with increased bleeding/thrombotic risk	Patients with increased events when compared to prior HRAE events will be assessed and tallied.	1 year
Hemocompatibility Score	A tiered hierarchal score that weighs each hemocompatibility related adverse event by its escalating clinical relevance will be recorded and scored. Mild events (e.g., ≤2 nonsurgical bleeding episodes) contribute a single point to the HCS, whereas serious events (e.g., disabling stroke) contribute a higher grade to the HCS (e.g., disabling stroke contributes 4 points). The score will be calculated for each patient by summing up all the points associated with each HRAE experienced by the patient for the duration of available follow-up. The minimum score is 0, and there is no maximum score. A higher score indicates more series thrombotic/bleeding related complications.	1 year

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: The University of Texas Health Science Center, Houston; Weill Medical College of Cornell University
• Investigators: Principal Investigator: Nir Uriel, MD, Seymour, Paul, and Gloria Milstein Professor of Cardiology at Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: October 22, 2024
• First Submitted That Met QC Criteria: October 22, 2024
• First Posted (Actual): October 23, 2024

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Embolism and Thrombosis; Pathological Conditions, Signs and Symptoms; Thrombosis; Hemorrhage; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrans; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Coumarins; Benzopyrans; Salicylates; Hydroxybenzoates; 4-Hydroxycoumarins; Aspirin; Warfarin; acarboxyprothrombin
• Other Study ID Numbers: AAAV3358

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No