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

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

Detailed Description
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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).

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

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Apixaban
* Drug: Warfarin
* Device: LVAD implant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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) Known bleeding within the last 30 days requiring emergency room presentation or hospitalization Known history of an inherited bleeding disorder (e.g., hemophilia, von Willebrand disease) Patients with active bleeding or a hemoglobin < 8.0 g/dl Total bilirubin > 2.0 mg/dl, shock liver, hepatic encephalopathy, or biopsy proven liver cirrhosis INR > 2.0 not due to anticoagulation therapy Platelet count <100,000 cells/mm3

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open-label, prospective, randomized, 1:1 intervention arm versus control
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LVAD, ventricular assist device, anticoagulation, apixaban, warfarin