Trial to Evaluate Anticoagulation Therapy in Hemodialysis Patients With Atrial Fibrillation

Phase 4

Completed

Conditions: Atrial Fibrillation
End Stage Renal Disease

Interventions: Drug: apixaban
Drug: warfarin

Registration Number: NCT02942407

Lead Sponsor: Christopher Granger, MD

Brief Summary: This is a prospective, randomized, open-label, blinded end-point evaluation trial. The patient population consists of patients on hemodialysis who have atrial fibrillation (AF) and end-stage renal disease (ESRD) .

Detailed Description: This is a multicenter study in adult patients with AF and ESRD who are on hemodialysis and who have stroke risk factors making them candidates for oral anticoagulation. Patients will be randomized to apixaban versus warfarin, and will be treated for up to 15 months.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 154

Inclusion Criteria

Males and females, age at least 18 years, or the local age of consent, whichever is greater.
Patients with AF defined as AF on ECG at enrollment or two or more reports of AF from separate monitoring events at least 2 weeks apart (report of ECG, Holter monitor, event monitor or implantable loop recorder).
CHA2DS2-VASc score of ≥ 2.
End-stage renal disease treated with hemodialysis for ≥ 3 months.
Considered by the treating physician(s) to be candidate for oral anticoagulation.
If of childbearing potential, be willing to avoid pregnancy during the study.

Exclusion Criteria

Not considered by the treating physician(s) to be candidates for oral anticoagulation (for example, hemoglobin < 8.5g/dL, history of intracranial hemorrhage, active bleeding, recent gastrointestinal bleed or retroperitoneal bleed, severe hepatic impairment, or anaphylactic reaction to apixaban)
Moderate or severe mitral stenosis
Conditions other than AF that require anticoagulation such as mechanical prosthetic valve, deep venous thrombosis, or pulmonary embolism
Need for aspirin at a dose > 81 mg a day or need for P2Y12 antagonist therapy (for example clopidogrel, prasugrel, or ticagrelor)
Life expectancy < 3 months
Anticipated kidney transplant within the next 3 months
Prisoners or others who are involuntarily incarcerated or detained
Pregnant, breastfeeding, or considering pregnancy.
Participation in a clinical trial of an experimental treatment within the past 30 days

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
apixaban	apixaban	apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients)
warfarin	warfarin	warfarin daily dose adjusted to target International Normalized Ration(INR) of 2-3

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing ISTH (International Society on Thrombosis and Haemostasis) Major or Clinically Relevant Non-major Bleeding	Randomization up to Month 15/Final Visit	Assess the safety of apixaban versus warfarin regarding ISTH major bleeding or clinically relevant non-major bleeding events in patients with NVAF (nonvalvular atrial fibrillation) and ESRD (end-stage renal disease) on hemodialysis. Major bleeding event is defined as:Acute clinically overt bleeding (including access site related bleeding) accompanied by 1 or more of the following: Decrease in Hgb of 2g/dL or more with overt bleeding; Transfusion of 2 or more units of packed RBCs in the setting of an overt bleeding event; Bleeding within a critical site. Hemorrhagic stroke (primary or infarction with hemorrhagic conversion) were classified as major bleeds. Non-major bleeding event is defined as: Acute or sub-acute clinically overt bleeding (including access site related bleeding) that does not meet criteria for major bleeding \& results in Hospital admission for bleeding, physician guided medical or surgical treatment for bleeding, or change in antithrombotic therapy

Secondary Outcome Measures

Name	Time	Method
Area Under the Plasma Apixaban Concentration Curve From 0 to 12 Hours After Dose (AUCO-12)	0-12 hours post-dose	Evaluate the pharmacokinetics of apixaban in ESRD NVAF patients on hemodialysis. The measurement was done from 0 to 12 hours after dose was given on Day 1.
Adherence to Treatment With Apixaban or With Warfarin	Month 15/Final Visit	Measured by self-reported days of medication compliance over the last 30 days.
Number of Participants Experiencing Mortality	Randomization up to Month 15/Final Visit	Evaluate mortality rates for those participants randomized to warfarin and apixaban in patients with NVAF and ESRD on hemodialysis
Persistence of Therapy	Randomization up to Month 15/Final Visit	Evaluate days between time from initiation to discontinuation of randomized therapy.
Apixaban Plasma Concentration, Cmax	0-12 hours post-dose	Evaluate the pharmacokinetics of apixaban in ESRD NVAF patients on hemodialysis. The measurement was done from 0-12 hours after the dose was given on Day 1.
Apixaban Pharmacodynamics, Chromogenic Factor Xa Assay	Baseline: Day 3, 4, or 5; Day 28	Evaluate the pharmacodynamics of apixaban in ESRD NVAF patients on hemodialysis
Apixaban Plasma Concentration, Cmin	0-12 hours post-dose	Evaluate the pharmacokinetics of apixaban in ESRD NVAF patients on hemodialysis. The measurement was done from 0-12 hours after the dose was given on Day 1.
Number of Participants Experiencing Stroke or Systemic Embolism	Randomization up to Month 15/Final Visit	Number of participants experiencing adjudicated stroke or systemic embolism.

Trial Locations

Locations (54): Nephrology Consultants
🇺🇸
Huntsville, Alabama, United States
The Medical Research Group, Inc.
🇺🇸
Fresno, California, United States
DaVita Clinical Trials, LLC
🇺🇸
Long Beach, California, United States
Southland Renal Medical Group
🇺🇸
Long Beach, California, United States
Valley Renal Medical Group Research
🇺🇸
Northridge, California, United States
Summit Nephrology Medical Group, Inc.
🇺🇸
Roseville, California, United States
Satellite Healthcare
🇺🇸
San Jose, California, United States
Washington Nephrology Associates
🇺🇸
Alexandria, Virginia, United States
South Florida Nephrology Group PA, Research Division
🇺🇸
Coral Springs, Florida, United States
LG. Diagnostic, Inc. & Cosmetic Center
🇺🇸
Miami, Florida, United States
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Nephrology Consultants
🇺🇸Huntsville, Alabama, United States