Bleeding, Heart Failure, Heart Transplant, LVAD (Left Ventricular Assist Device) Thrombosis, Stroke, Thrombosis; Artery
Conditions
Brief summary
This study is being done to learn the safety and efficacy of a new anticoagulant therapy with apixaban as compared to warfarin to prevent thrombotic events while protecting from bleeding complications in patients with advanced heart failure who are chronically supported by a HeartMate 3 Left Ventricular Assist Device for 3 months.
Detailed description
Heart failure is a global epidemic, and Left Ventricular Assist Devices (LVADs) - particularly the HeartMate 3 (HM3) - are increasingly used due to their survival benefit over medical therapy. Despite advances, hemocompatibility-related adverse events (HRAEs) like thrombosis and bleeding remain significant causes of morbidity and mortality. Direct Oral Anticoagulants (DOACs) have shown superiority over warfarin in heart failure patients, with lower rates of embolic and intracranial bleeding. Reduced-dose DOACs also appear to reduce major bleeding without increasing thrombotic risk. However, data on their use in LVAD patients is limited, consisting mainly of case reports, small series, retrospective analyses, and a few small randomized clinical trials. Some reports suggest apixaban may reduce bleeding in high-risk LVAD patients, though cases of pump thrombosis and stroke have occurred. Early studies comparing DOACs to warfarin in patients with HeartMate II (HMII), HeartWare™ HVAD™ System, and The Abbott HeartMate 3 (HM3) show no significant differences in outcomes, with a trend toward less bleeding with apixaban. Two small randomized clinical trials in HM3 patients (The DOAC LVAD Study and The DOT-HM3 Study) found similar results. This prospective, randomized, controlled, non-inferiority trial will evaluate the safety and efficacy of apixaban versus vitamin K antagonists in HM3 patients more than 3 months post-implant.
Interventions
DRUGWarfarin
Warfarin dose titrated for an International Normalized Ratio (INR) \>= 1.8
DRUGApixaban
Apixaban 5 mg bid (twice a day)
Sponsors
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participants will have HeartMate3 LVAD implanted \> 3 months before enrollment * ≥ 18 years old * Treated with WARFARIN SODIUM * Participant must provide written informed consent prior to any clinical investigation related procedure * In female participants of childbearing capability, not currently pregnant and on appropriate contraception
Exclusion criteria
* Participation in any other clinical investigation(s) involving a Mechanical Circulatory Support (MCS) device, or interventional investigation(s) likely to confound study results or affect study outcome * Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results * Known allergy to Apixaban * Bridge to transplant * Severe renal dysfunction Estimated Glomerular Filtration Rate (eGFR) \<20 * History of major bleeding event with subsequent reduction of INR goal to \< 1.8 * Apixaban dose reduction criteria (Age ≥80 years, weight ≤60 kg, creatinine ≥1.5 mg/dL) * Aortic root thrombus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival free of major hemocompatibility related adverse event | 12 months | Major Hemocompatibility Related Adverse Event: Stroke, Pump Thrombosis, major non surgical Bleeding (moderate or severe), Arterial Peripheral Thromboembolism. Rates will be compared between study groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-surgical Major Hemorrhagic Events | 12 months | Rates will be compared between study groups. |
| Non-surgical Major Thrombotic Events | 12 months | Rates will be compared between study groups. |
| Survival | 12 months | Rates will be compared between study groups. |
| Stroke Rates | 12 months | Rates will be compared between study groups. |
| Pump Thrombosis Rates | 12 months | Rates will be compared between study groups. |
| Bleeding Rates | 12 months | Rates will be compared between study groups. |
| Rates of listing for Heart Transplant | 12 months | Rates will be compared between study groups. |
Contacts
CONTACTIlan Richter, MD
PRINCIPAL_INVESTIGATORNir Uriel, MD
New York Presbyterian / Columbia University Medical Center
Outcome results
None listed