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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04865978

Acronym

DOAC LVAD

Enrollment

Registered

2021-04-29

Start date

2021-12-14

Completion date

2023-11-07

Last updated

2024-11-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heart Failure

Keywords

ventricular assist device, LVAD, anticoagulation, apixaban, warfarin

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).

Interventions

DRUGApixaban

Patients randomized to apixaban will be started on a dose of 5 mg BID.

DRUGWarfarin

Patients randomized to warfarin will be started on a dose per institutional protocol and titrated to an INR goal of 2.0 - 2.5.

DEVICELVAD implant

Subjects will undergo HeartMate 3 LVAD implant prior to randomization

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

NONE

Intervention model description

Open-label, prospective, randomized, 1:1 intervention arm versus control

Eligibility

Sex/Gender

ALL

Age

18 Years to 99 Years

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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 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
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 Gastrointestinal Bleeding	From enrollment to end of treatment at 24 weeks	Compared between each study arm

Other

Measure	Time frame	Description
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	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) evaluated in subgroups of patients within 3 months of implant versus greater than 3 months from LVAD implant

Countries

United States

Participant flow

Participants by arm

Arm	Count
Apixaban LVAD patients randomized to the experimental arm will be prescribed apixaban 5 mg twice daily. Apixaban: Patients randomized to apixaban will be started on a dose of 5 mg BID. LVAD implant: Subjects will undergo HeartMate 3 LVAD implant prior to randomization	16
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 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. LVAD implant: Subjects will undergo HeartMate 3 LVAD implant prior to randomization	14
Total	30

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	One patient did not complete the study due to infection and device explant	1	0

Baseline characteristics

Characteristic	Warfarin	Total	Apixaban
Age, Continuous	56 years	60 years	64 years
Race/Ethnicity, Customized Race or Ethnic Group Asian	1 Participants	2 Participants	1 Participants
Race/Ethnicity, Customized Race or Ethnic Group Black	11 Participants	14 Participants	3 Participants
Race/Ethnicity, Customized Race or Ethnic Group Other	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Race or Ethnic Group White	2 Participants	13 Participants	11 Participants
Sex: Female, Male Female	0 Participants	2 Participants	2 Participants
Sex: Female, Male Male	14 Participants	28 Participants	14 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 16	0 / 14
other Total, other adverse events	14 / 16	12 / 14
serious Total, serious adverse events	7 / 16	8 / 14

Outcome results

Primary

Freedom From Death or Hemocompatibility Related Adverse Events (Stroke, Device Thrombosis, Bleeding, Aortic Root Thrombus, and Arterial Non-CNS Thromboembolism)

Freedom from death or hemocompatibility related adverse events (composite of stroke, device thrombosis, bleeding, aortic root thrombus, and arterial non-CNS thromboembolism)