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

Palak Shah

Status and phase: Completed; Phase 2

Conditions: Heart Failure

Treatments: Drug: Apixaban; Drug: Warfarin; Device: LVAD implant

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04865978

U21-06-4470

Details and patient eligibility

About

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

Full 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).

Enrollment: 30 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

Apixaban

Experimental group

Description:

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

Treatment:

Device: LVAD implant

Drug: Apixaban

Warfarin

Active Comparator group

Description:

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

Treatment:

Device: LVAD implant

Drug: Warfarin