Clinical trial NCT04865978: Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices
Official title: Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Keywords: ventricular assist device
LVAD
anticoagulation
apixaban
warfarin
Lead sponsor: Inova Health Care Services
Sponsor class: OTHER
Collaborators: name: Abbott Medical Devices
First posted: 2021-04-29
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, prospective, randomized, 1:1 intervention arm versus control
Primary purpose: SUPPORTIVE_CARE

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).

Eligibility criteria: 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

Primary outcomes:
measure: Freedom From Death or Hemocompatibility Related Adverse Events (Stroke, Device Thrombosis, Bleeding, Aortic Root Thrombus, and Arterial Non-CNS Thromboembolism)
timeFrame: From enrollment to end of treatment at 24 weeks
Secondary outcomes:
measure: Survival Free of Any Stroke
timeFrame: From enrollment to end of treatment at 24 weeks
measure: Survival Free of Ischemic Stroke
timeFrame: From enrollment to end of treatment at 24 weeks
measure: Survival Free of Hemorrhagic Stroke
timeFrame: From enrollment to end of treatment at 24 weeks
measure: Survival Free of Device Thrombosis
timeFrame: From enrollment to end of treatment at 24 weeks
measure: Survival Free of Gastrointestinal Bleeding
timeFrame: From enrollment to end of treatment at 24 weeks
measure: Survival Free of Major Non-gastrointestinal Bleeding
timeFrame: From enrollment to end of treatment at 24 weeks
measure: All-cause Mortality
timeFrame: From enrollment to end of treatment at 24 weeks
measure: Cardiovascular Mortality
timeFrame: From enrollment to end of treatment at 24 weeks
measure: Survival Free of Aortic Root Thrombus
timeFrame: From enrollment to end of treatment at 24 weeks
Other outcomes:
measure: 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
timeFrame: From enrollment to end of treatment at 24 weeks
Locations:
city: Falls Church
country: United States
facility: Inova Fairfax Medical Campus
state: Virginia
Study officials:
affiliation: Inova Health Care Services
name: Palak Shah, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.