Skip to main content
OpenTrials
Completed

NCT Number: NCT02942407

Trial to Evaluate Anticoagulation Therapy in Hemodialysis Patients With Atrial Fibrillation

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) .

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Atrial Fibrillation Arrhythmias, Cardiac Cardiovascular Diseases Chronic Disease Disease Attributes End Stage Renal Disease Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Heart Diseases Kidney Diseases Kidney Failure, Chronic Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Nephrology Consultants, Huntsville, Alabama, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Apixaban

Drug

oral anticoagulant

Other names: Eliquis

Warfarin

Drug

oral anticoagulant

Other names: Coumadin, Jantoven

Primary outcomes

  1. Number of Participants Experiencing ISTH (International Society on Thrombosis and Haemostasis) Major or Clinically Relevant Non-major Bleeding

    Time frame: 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 outcomes

  1. Number of Participants Experiencing Stroke or Systemic Embolism

    Time frame: Randomization up to Month 15/Final Visit

    Number of participants experiencing adjudicated stroke or systemic embolism.

  2. Number of Participants Experiencing Mortality

    Time frame: 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

  3. Persistence of Therapy

    Time frame: Randomization up to Month 15/Final Visit

    Evaluate days between time from initiation to discontinuation of randomized therapy.

  4. Apixaban Plasma Concentration, Cmax

    Time frame: 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.

  5. Apixaban Plasma Concentration, Cmin

    Time frame: 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.

  6. Area Under the Plasma Apixaban Concentration Curve From 0 to 12 Hours After Dose (AUCO-12)

    Time frame: 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.

  7. Apixaban Pharmacodynamics, Chromogenic Factor Xa Assay

    Time frame: Baseline: Day 3, 4, or 5; Day 28

    Evaluate the pharmacodynamics of apixaban in ESRD NVAF patients on hemodialysis

  8. Adherence to Treatment With Apixaban or With Warfarin

    Time frame: Month 15/Final Visit

    Measured by self-reported days of medication compliance over the last 30 days.

Other outcomes

  1. Number of Participants Experiencing Systemic Embolism

    Time frame: Randomization up to Month 15/Final Visit

    Adjudicated diagnosis of systemic arterial embolism (Non-pulmonary, non-cranial events) will require a positive clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries), which is supported by evidence of embolism/thrombosis from surgical specimens, autopsy, angiography, vascular imaging, or other objective testing.

    Clinical presentation would include:

    • Abrupt development of pain, absent pulses, pallor, and/or paresis in an extremity (at least an entire digit) without previous severe claudication or findings of severe peripheral vascular disease.
    • Renal embolism will be diagnosed when sudden flank pain or a change in renal laboratory findings occurred.
    • Abdominal vascular/visceral embolism was considered definite if acute abdominal symptoms or referred symptoms developed along with a change in abdominal examination or appropriate laboratory values.

  2. Number of Participants Experiencing Stroke

    Time frame: Randomization up to Month 15/Final Visit

    Adjudcated stroke defined as a new, non-traumatic episode of focal or global neurological dysfunction of sudden onset caused by central nervous system (CNS) vascular injury as a result of hemorrhage or infarction and not due to a readily identifiable non-vascular cause (i.e. brain tumor). CNS includes brain, spinal cord and retina. The required duration of the deficit is ≥ 24 hours.

    • Events with neurologic deficit lasting for < 24 hours and an imaging modality showing evidence of an acute stroke will be counted as stroke as well.
    • A retinal ischemic event (embolism, infarction) will be considered a stroke

  3. Number of Participants Experiencing Stroke, Systemic Embolism, Major Bleeding or All-cause Mortality

    Time frame: Randomization up to Month 15/Final Visit

    Evaluate those experiencing stroke, systemic embolism, ISTH major bleeding, or all-cause mortality for those randomized to warfarin and apixaban in patients with NVAF and ESRD on hemodialysis

    Definitions of stroke and systemic embolism are provided under the measurement description of the secondary outcomes for each individual event. Definition of major bleed is provided in outcome measurement description of the primary outcome measure.

  4. Baseline Biomarkers

    Time frame: Baseline

    Analysis of outcomes and treatment effect according to levels of cardiovascular biomarkers at baseline

Sponsors and collaborators

Lead sponsor

Christopher Granger, MD

Other

Collaborators

  • Bristol-Myers Squibb

Registry information

Official study title

RENal Hemodialysis Patients ALlocated Apixaban Versus Warfarin in Atrial Fibrillation (RENAL-AF) Randomized Clinical Trial

Acronym: RENAL-AF

Important dates

Study start
2016
Primary completion
2019
Study completion
2019
First posted
Oct 24, 2016
Registry last updated
Dec 29, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.