Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices (DOAC LVAD)

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

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Apixaban; Device: LVAD implant; Drug: Warfarin

Detailed Description

This pilot study will be a prospective, randomized, controlled, open label, trial of HeartMate 3 (HM3) LVAD patients with 1:1 randomization to either apixaban or warfarin. All patients will be treated with aspirin 81 mg daily as per the LVAD manufacturer instructions for use (IFU).

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. History of post-LVAD device thrombosis, stroke, or gastrointestinal bleeding
2. Patients who are bridge to transplant and a current UNOS status 1-3
3. Ongoing inotrope therapy after LVAD (e.g., milrinone, dobutamine, epinephrine)
4. Permanent right ventricular assist device at the time of LVAD implant
5. Patients with a mechanical heart valve
6. Patients with end-stage renal disease on dialysis
7. Pregnant patients
8. Known history of ischemic stroke, intracranial bleed, or neurosurgery within 3 months
9. Known history of intracerebral arteriovenous malformation, cerebral aneurysm or mass lesions of the central nervous system.
10. Recent (<48 hours) or planned spinal or epidural anesthesia or puncture
11. 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.
12. Thrombolysis within the previous 7 days
13. Patients with an allergy or contraindication to aspirin, warfarin, or apixaban
14. Patients on antiplatelet therapy other than aspirin (e.g., clopidogrel, prasugrel, ticagrelor, dipyridamole, or pentoxifylline)
15. Patients on combined P-glycoprotein and strong CPY3A4 inhibitors or inducers (e.g., fluconazole, posaconazole, rifampin)
16. Known bleeding within the last 30 days requiring emergency room presentation or hospitalization
17. Known history of an inherited bleeding disorder (e.g., hemophilia, von Willebrand disease)
18. Patients with active bleeding or a hemoglobin < 8.0 g/dl
19. Total bilirubin > 2.0 mg/dl, shock liver, hepatic encephalopathy, or biopsy proven liver cirrhosis
20. INR > 2.0 not due to anticoagulation therapy
21. Platelet count <100,000 cells/mm3

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apixaban; LVAD patients randomized to the experimental arm will be prescribed apixaban 5 mg twice daily.	Drug: Apixaban; Patients randomized to apixaban will be started on a dose of 5 mg BID.; Device: LVAD implant; Subjects will undergo HeartMate 3 LVAD implant prior to randomization
Active Comparator: Warfarin; LVAD patients randomized to the control arm will be prescribed warfarin which will be dosed to achieve an INR goal of 2-2.5	Device: LVAD implant; Subjects will undergo HeartMate 3 LVAD implant prior to randomization; Drug: Warfarin; Patients randomized to warfarin will be started on a dose per institutional protocol and titrated to an INR goal of 2.0 - 2.5.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from death or hemocompatibility related adverse events (stroke, device thrombosis, bleeding, aortic root thrombus, and arterial non-CNS thromboembolism)	Composite endpoint in each arm	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival free of any stroke	Compared between each study arm	24 weeks
Survival free of ischemic stroke	Compared between each study arm	24 weeks
Survival free of hemorrhagic stroke	Compared between each study arm	24 weeks
Survival free of device thrombosis	Compared between each study arm	24 weeks
Survival free of gastrointestinal bleeding	Compared between each study arm	24 weeks
Survival free of major non-gastrointestinal bleeding	Compared between each study arm	24 weeks
All-cause mortality	Compared between each study arm	24 weeks
Cardiovascular mortality	Compared between each study arm	24 weeks
Survival free of aortic root thrombus	Compared between each study arm	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of primary and secondary outcomes will be evaluated in subgroups of patients within 3 months of implant versus greater than 3 months from LVAD implant	Compared between each study arm	24 weeks

Collaborators and Investigators

• Sponsor: Palak Shah
• Collaborators: Abbott Medical Devices
• Investigators: Principal Investigator: Palak Shah, MD, MS, Inova Health Care Services

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2021
• Primary Completion (Actual): October 5, 2023
• Study Completion (Actual): November 7, 2023

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: April 28, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: warfarin; anticoagulation; apixaban; LVAD; ventricular assist device
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Apixaban; Warfarin
• Other Study ID Numbers: U21-06-4470

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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