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

NCT07081035 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: AMC_2025_2573
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

HeartMate 3 LVAD; Left Ventricular Assist Device; Advanced Heart Failure; Anticoagulation; Warfarin; International Normalized Ratio (INR); Low-intensity Anticoagulation; Major Bleeding; Gastrointestinal Bleeding; Pump Thrombosis; Stroke; Thromboembolism; Hemocompatibility; Randomized Controlled Trial; Safety and Efficacy

Outcome Measures

Primary Outcomes (1)

• Incidence of composite hemocompatibility-related events

  The primary outcome is defined as a composite of hemocompatibility-related events including major bleeding (INTERMACS major bleeding criteria), stroke (ischemic or hemorrhagic), and pump thrombosis occurring within 6 months post-randomization. Events will be centrally adjudicated based on standardized INTERMACS definitions.

  Within 6 months after randomization

Secondary Outcomes (18)

• All-cause mortality

  Within 6 months after randomization

• Cardiac death

  Within 6 months after randomization

• LVAD pump thrombosis

  Within 6 months after randomization

• LVAD-related thromboembolism

  Within 6 months after randomization

• Transient ischemic attack (TIA)

  Within 6 months after randomization

Study Arms (2)

Low-intensity INR group

EXPERIMENTAL

Intervention: Drug: Warfarin (INR 1.5-2.0)

Drug: Warfarin (low-intensity anticoagulation)

Standard INR group

ACTIVE COMPARATOR

Intervention: Drug: Warfarin (INR 2.0-3.0)

Drug: Warfarin (standard anticoagulation)

Interventions

Warfarin (low-intensity anticoagulation) DRUG

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.

Low-intensity INR group

Warfarin (standard anticoagulation) DRUG

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.

Standard INR group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who meet all of the following criteria will be eligible for randomization:
• Adults aged ≥19 years who have successfully undergone implantation of a HeartMate 3 LVAD.
• Patients who are at least 30 days post-implantation of HeartMate 3 LVAD.
• Patients who have maintained stable anticoagulation therapy with standard INR (2.0-3.0) for at least 30 days post-LVAD implantation.
• Patients or their legal representatives who provide documented informed consent and agree to the study protocol and follow-up schedule.

You may not qualify if:

• Patients who meet any of the following criteria will be excluded:
• Patients implanted with any mechanical assist device other than HeartMate 3 LVAD (e.g., other LVAD models, RVAD, BiVAD).
• Patients with a clinically significant stroke or transient ischemic attack (TIA) within the past 6 months.
• Patients with a history of hemorrhagic stroke.
• Patients who experienced major bleeding events within the past 6 months (based on INTERMACS major bleeding criteria).
• Patients with uncontrolled severe hypertension (systolic ≥180 mmHg or diastolic ≥110 mmHg).
• Patients requiring active treatment or surgical intervention for acute LVAD-related thrombosis or hemodynamic instability, or patients who underwent LVAD-related reoperation within the past 30 days.
• Patients with severe renal dysfunction (estimated Glomerular Filtration Rate \<15 mL/min) or patients undergoing dialysis.
• Patients with severe liver dysfunction causing coagulation abnormalities or those classified as Child-Pugh class B or C.
• Patients with active bleeding or ongoing hemorrhagic conditions.
• Patients with a high bleeding risk due to:
• Gastrointestinal bleeding or ulcers within the past 6 months.
• Surgery involving the brain, spine, or eyes within the past 6 months.
• Major central nervous system, ophthalmologic, or major open surgical procedures within the past 6 months.
• Presence or suspicion of esophageal varices.

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center, University of Ulsan College of Medicine

Seoul, 05505, South Korea

Location

Related Publications (5)

• Netuka I, Ivak P, Tucanova Z, Gregor S, Szarszoi O, Sood P, Crandall D, Rimsans J, Connors JM, Mehra MR. Evaluation of low-intensity anti-coagulation with a fully magnetically levitated centrifugal-flow circulatory pump-the MAGENTUM 1 study. J Heart Lung Transplant. 2018 May;37(5):579-586. doi: 10.1016/j.healun.2018.03.002. Epub 2018 Apr 11.

  PMID: 29655662 BACKGROUND

• Rogers JG, Pagani FD, Tatooles AJ, Bhat G, Slaughter MS, Birks EJ, Boyce SW, Najjar SS, Jeevanandam V, Anderson AS, Gregoric ID, Mallidi H, Leadley K, Aaronson KD, Frazier OH, Milano CA. Intrapericardial Left Ventricular Assist Device for Advanced Heart Failure. N Engl J Med. 2017 Feb 2;376(5):451-460. doi: 10.1056/NEJMoa1602954.

  PMID: 28146651 BACKGROUND

• Desai SR, Hwang NC. 2023 ISHLT Guidelines for Mechanical Circulatory Support. J Cardiothorac Vasc Anesth. 2023 Dec;37(12):2419-2422. doi: 10.1053/j.jvca.2023.07.044. Epub 2023 Aug 8. No abstract available.

  PMID: 37659882 BACKGROUND

• Mehra MR, Naka Y, Uriel N, Goldstein DJ, Cleveland JC Jr, Colombo PC, Walsh MN, Milano CA, Patel CB, Jorde UP, Pagani FD, Aaronson KD, Dean DA, McCants K, Itoh A, Ewald GA, Horstmanshof D, Long JW, Salerno C; MOMENTUM 3 Investigators. A Fully Magnetically Levitated Circulatory Pump for Advanced Heart Failure. N Engl J Med. 2017 Feb 2;376(5):440-450. doi: 10.1056/NEJMoa1610426. Epub 2016 Nov 16.

  PMID: 27959709 BACKGROUND

• Mehra MR, Goldstein DJ, Uriel N, Cleveland JC Jr, Yuzefpolskaya M, Salerno C, Walsh MN, Milano CA, Patel CB, Ewald GA, Itoh A, Dean D, Krishnamoorthy A, Cotts WG, Tatooles AJ, Jorde UP, Bruckner BA, Estep JD, Jeevanandam V, Sayer G, Horstmanshof D, Long JW, Gulati S, Skipper ER, O'Connell JB, Heatley G, Sood P, Naka Y; MOMENTUM 3 Investigators. Two-Year Outcomes with a Magnetically Levitated Cardiac Pump in Heart Failure. N Engl J Med. 2018 Apr 12;378(15):1386-1395. doi: 10.1056/NEJMoa1800866. Epub 2018 Mar 11.

  PMID: 29526139 BACKGROUND

MeSH Terms

Conditions

Gastrointestinal Hemorrhage; Stroke; Thromboembolism

Interventions

Warfarin

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Min-Seok Kim, MD, PhD

CONTACT

+82-2-3010-5416; msk@amc.seoul.kr

Kitae Kim, MD

CONTACT

+82-2-3010-0987; kktae0416@naver.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 15, 2025
• First Posted: July 23, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: July 23, 2025

Record last verified: 2025-07

Locations

KR (1)