Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices

NCT04865978 | Completed Phase 2 Results DMC FDA Drug FDA Device

• 1 other identifier: U21-06-4470
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Prospective, randomized, controlled, open label, trial of LVAD patients with 1:1 randomization to either apixaban or warfarin.

Conditions

Heart Failure

Keywords

ventricular assist device; LVAD; anticoagulation; apixaban; warfarin

Outcome Measures

Primary Outcomes (1)

• Freedom From Death or Hemocompatibility Related Adverse Events (Stroke, Device Thrombosis, Bleeding, Aortic Root Thrombus, and Arterial Non-CNS Thromboembolism)

  Freedom from death or hemocompatibility related adverse events (composite of stroke, device thrombosis, bleeding, aortic root thrombus, and arterial non-CNS thromboembolism)

  From enrollment to end of treatment at 24 weeks

Secondary Outcomes (9)

• Survival Free of Any Stroke

  From enrollment to end of treatment at 24 weeks

• Survival Free of Ischemic Stroke

  From enrollment to end of treatment at 24 weeks

• Survival Free of Hemorrhagic Stroke

  From enrollment to end of treatment at 24 weeks

• Survival Free of Device Thrombosis

  From enrollment to end of treatment at 24 weeks

• Survival Free of Gastrointestinal Bleeding

  From enrollment to end of treatment at 24 weeks

Other Outcomes (1)

• Freedom From Death or Hemocompatibility Related Adverse Events Evaluated in Subgroups of Patients Within 3 Months of Implant Versus Greater Than 3 Months From LVAD Implant

  From enrollment to end of treatment at 24 weeks

Study Arms (2)

Apixaban

EXPERIMENTAL

LVAD patients randomized to the experimental arm will be prescribed apixaban 5 mg twice daily.

Drug: Apixaban; Device: LVAD implant

Warfarin

ACTIVE COMPARATOR

LVAD patients randomized to the control arm will be prescribed warfarin which will be dosed to achieve an INR goal of 2-2.5

Drug: Warfarin; Device: LVAD implant

Interventions

Apixaban DRUG

Patients randomized to apixaban will be started on a dose of 5 mg BID.

Apixaban

Warfarin DRUG

Patients randomized to warfarin will be started on a dose per institutional protocol and titrated to an INR goal of 2.0 - 2.5.

Warfarin

LVAD implant DEVICE

Subjects will undergo HeartMate 3 LVAD implant prior to randomization

Apixaban; Warfarin

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients implanted with a HeartMate 3 LVAD
• Age 18 or greater and able to provide written informed consent
• Females of childbearing age must agree to adequate contraception

You may not qualify if:

• History of post-LVAD device thrombosis, stroke, or gastrointestinal bleeding
• Patients who are bridge to transplant and a current UNOS status 1-3
• Ongoing inotrope therapy after LVAD (e.g., milrinone, dobutamine, epinephrine)
• Permanent right ventricular assist device at the time of LVAD implant
• Patients with a mechanical heart valve
• Patients with end-stage renal disease on dialysis
• Pregnant patients
• Known history of ischemic stroke, intracranial bleed, or neurosurgery within 3 months
• Known history of intracerebral arteriovenous malformation, cerebral aneurysm or mass lesions of the central nervous system.
• Recent (\<48 hours) or planned spinal or epidural anesthesia or puncture
• Prior history of known thrombophilia (e.g., factor V Leiden, prothrombin gene mutation, protein C or S deficiency, antithrombin 3 deficiency, hyperhomocysteinemia, antiphospholipid antibody syndrome) or indication for higher INR goal (\>2.5) with warfarin.
• Thrombolysis within the previous 7 days
• Patients with an allergy or contraindication to aspirin, warfarin, or apixaban
• Patients on antiplatelet therapy other than aspirin (e.g., clopidogrel, prasugrel, ticagrelor, dipyridamole, or pentoxifylline)
• Patients on combined P-glycoprotein and strong CPY3A4 inhibitors or inducers (e.g., fluconazole, posaconazole, rifampin)

Sponsors & Collaborators

• Palak Shah: lead
• Abbott Medical Devices: collaborator

Study Sites (1)

Inova Fairfax Medical Campus

Falls Church, Virginia, 22042, United States

Location

Related Publications (2)

• Dimond M, Looby M, Shah B, Sinha SS, Isseh I, Rollins AT, Abdul-Aziz AA, Kennedy J, Tang DG, Klein KM, Casselman S, Vermeulen C, Sheaffer W, Snipes M, O'connor CM, Shah P. Design and Rationale for the Direct Oral Anticoagulant Apixaban in Left Ventricular Assist Devices (DOAC LVAD) Study. J Card Fail. 2024 Jun;30(6):819-828. doi: 10.1016/j.cardfail.2023.10.473. Epub 2023 Nov 11.

  PMID: 37956897 BACKGROUND

• Shah P, Looby M, Dimond M, Bagchi P, Shah B, Isseh I, Rollins AT, Abdul-Aziz AA, Kennedy J, Tang DG, Klein KM, Casselman S, Vermeulen C, Sheaffer W, Snipes M, Sinha SS, O'Connor CM. Evaluation of the Hemocompatibility of the Direct Oral Anticoagulant Apixaban in Left Ventricular Assist Devices: The DOAC LVAD Study. JACC Heart Fail. 2024 Sep;12(9):1540-1549. doi: 10.1016/j.jchf.2024.04.013. Epub 2024 May 7.

  PMID: 38795110 RESULT

MeSH Terms

Conditions

Heart Failure

Interventions

apixaban; Warfarin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Palak Shah
• Organization: Inova Schar Heart and Vascular

palak.shah@inova.org

703-776-2213

Study Officials

• Palak Shah, MD, MS

  Inova Health Care Services

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Director, Mechanical Circulatory Support

Model Details: Open-label, prospective, randomized, 1:1 intervention arm versus control

Study Record Dates

• First Submitted: April 26, 2021
• First Posted: April 29, 2021
• Study Start: December 14, 2021
• Primary Completion: October 5, 2023
• Study Completion: November 7, 2023
• Last Updated: November 14, 2024
• Results First Posted: November 14, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)