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

Phase 2

Completed

• Conditions: Heart Failure
• Interventions: Drug: Apixaban; Drug: Warfarin; Device: LVAD implant

• Registration Number: NCT04865978
• Lead Sponsor: Palak Shah

Brief Summary

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

• Study First Submitted: 2021-04-26
• Study First Submitted QC: 2021-04-28
• Study First Posted: 2021-04-29
• Study Start: 2021-12-14
• Primary Completion: 2023-10-05
• Study Completion: 2023-11-07
• Status Verified: 2024-10
• Results First Submitted: 2024-10-21
• Results First Submitted QC: 2024-10-21
• Last Update Submitted: 2024-10-21
• Results First Posted: 2024-11-14
• Last Update Posted: 2024-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Apixaban	LVAD implant	LVAD patients randomized to the experimental arm will be prescribed apixaban 5 mg twice daily.
Warfarin	LVAD implant	LVAD patients randomized to the control arm will be prescribed warfarin which will be dosed to achieve an INR goal of 2-2.5
Apixaban	Apixaban	LVAD patients randomized to the experimental arm will be prescribed apixaban 5 mg twice daily.
Warfarin	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

Primary Outcome Measures

Name	Time	Method
Freedom From Death or Hemocompatibility Related Adverse Events (Stroke, Device Thrombosis, Bleeding, Aortic Root Thrombus, and Arterial Non-CNS Thromboembolism)	From enrollment to end of treatment at 24 weeks	Freedom from death or hemocompatibility related adverse events (composite of stroke, device thrombosis, bleeding, aortic root thrombus, and arterial non-CNS thromboembolism)

Secondary Outcome Measures

Name	Time	Method
Survival Free of Hemorrhagic Stroke	From enrollment to end of treatment at 24 weeks	Compared between each study arm
Survival Free of Device Thrombosis	From enrollment to end of treatment at 24 weeks	Compared between each study arm
Survival Free of Gastrointestinal Bleeding	From enrollment to end of treatment at 24 weeks	Compared between each study arm
Survival Free of Major Non-gastrointestinal Bleeding	From enrollment to end of treatment at 24 weeks	Compared between each study arm
All-cause Mortality	From enrollment to end of treatment at 24 weeks	Compared between each study arm
Cardiovascular Mortality	From enrollment to end of treatment at 24 weeks	Compared between each study arm
Survival Free of Aortic Root Thrombus	From enrollment to end of treatment at 24 weeks	Compared between each study arm
Survival Free of Any Stroke	From enrollment to end of treatment at 24 weeks	Compared between each study arm
Survival Free of Ischemic Stroke	From enrollment to end of treatment at 24 weeks	Compared between each study arm

Trial Locations

Locations (1)

Inova Fairfax Medical Campus; 🇺🇸 Falls Church, Virginia, United States