Trial of Low-intensity Anticoagulation to Reduce GI or Other Bleeding Complications With Equivalent Therapeutic Efficacy in HeartMate 3 LVAD Patients

Summary

The TARGET trial is a prospective, single-center, randomized, open-label, active-controlled inequality clinical trial designed to evaluate the safety and efficacy of low-intensity anticoagulation therapy (target INR 1.5-2.0) compared to standard anticoagulation therapy (target INR 2.0-3.0) in patients receiving a HeartMate 3 Left Ventricular Assist Device (LVAD).

Despite the demonstrated effectiveness of HeartMate 3 LVAD in reducing thromboembolic complications, standard anticoagulation treatment guidelines recommend maintaining an INR between 2.0 and 3.0, which can lead to a substantial risk of bleeding, especially gastrointestinal (GI) bleeding. Preliminary studies, such as MAGENTUM 1, have indicated potential safety and reduced bleeding events at lower INR targets (1.5-1.9). However, robust evidence through randomized controlled trials is still required.

The primary objective of the TARGET trial is to determine if low-intensity anticoagulation therapy significantly reduces the incidence of major bleeding and thrombotic events compared to standard therapy within 6 months post-randomization. Secondary objectives include evaluating the safety and hematological complications associated with low-intensity anticoagulation.

The study will enroll adult patients aged ≥19 years who have been stably maintained on standard INR therapy (2.0-3.0) for at least 30 days post-HeartMate 3 LVAD implantation. Participants will be randomized in a 1:1 ratio into two groups: the low-intensity INR group (target INR 1.5-2.0) and the standard INR group (target INR 2.0-3.0). Randomization will be stratified based on the presence of atrial fibrillation.

The primary endpoint is a composite of hemocompatibility-related events, including major bleeding, stroke, and pump thrombosis, occurring within 6 months after randomization, as defined by INTERMACS criteria. Secondary endpoints encompass clinical outcomes such as all-cause mortality, cardiac death, LVAD-related thromboembolic events, stroke, systemic embolism, myocardial infarction, major bleeding incidents, and the rate and number of LVAD-related hospital readmissions and reoperations. Additionally, INR management outcomes, including time in therapeutic range (TTR) and frequency of warfarin dose adjustments, will be assessed.

The trial duration is approximately 36 months, including a 24-month enrollment period, a 6-month follow-up period for each participant, and time allocated for data analysis and reporting. Safety will be rigorously monitored by a Data Safety Monitoring Board (DSMB) and Clinical Events Committee (CEC), ensuring participant safety and data integrity throughout the study.

This trial aims to provide critical insights that could optimize anticoagulation strategies in LVAD patients, potentially improving patient safety by reducing bleeding risks without compromising thrombotic event protection.

Conditions

• Advanced Heart Failure
• Left Ventricular Assist Devices
• Anticoagulation Treatment
• Bleeding Complications
• Thrombotic Complications

Interventions

DRUG

Warfarin (low-intensity anticoagulation)

Low-intensity INR group (Experimental): Participants will receive anticoagulation therapy with warfarin, aiming for a reduced INR range of 1.5-2.0, which is lower than the current standard recommendation. Warfarin dosing will be regularly adjusted based on INR monitoring throughout the 6-month study period.

DRUG

Warfarin (standard anticoagulation)

Standard INR group (Active Comparator): Participants will receive anticoagulation therapy with warfarin, maintaining an INR within the standard therapeutic range of 2.0-3.0. Warfarin dosing adjustments will be made regularly according to standard clinical practice and INR monitoring throughout the 6-month study period.

Sponsors & Collaborators

• Asan Medical Center

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

19 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-10-31

Primary Completion

2028-10-31

Completion

2029-01-31

Countries

• South Korea

Study Locations