Trial to Evaluate Anticoagulation Therapy in Hemodialysis Patients With Atrial Fibrillation (RENAL-AF)
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|ClinicalTrials.gov Identifier: NCT02942407|
Recruitment Status : Completed
First Posted : October 24, 2016
Results First Posted : December 29, 2020
Last Update Posted : December 29, 2020
|Condition or disease||Intervention/treatment||Phase|
|Atrial Fibrillation End Stage Renal Disease||Drug: apixaban Drug: warfarin||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||154 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||RENal Hemodialysis Patients ALlocated Apixaban Versus Warfarin in Atrial Fibrillation (RENAL-AF) Randomized Clinical Trial|
|Actual Study Start Date :||December 2016|
|Actual Primary Completion Date :||July 27, 2019|
|Actual Study Completion Date :||August 12, 2019|
apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients)
Other Name: Eliquis
warfarin daily dose adjusted to target International Normalized Ration(INR) of 2-3
- 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
- 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.
- 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
- Persistence of Therapy [ Time Frame: Randomization up to Month 15/Final Visit ]Evaluate days between time from initiation to discontinuation of randomized therapy.
- 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.
- 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.
- 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.
- 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
- 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.
- 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.
- 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
- 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.
- Baseline Biomarkers [ Time Frame: Baseline ]Analysis of outcomes and treatment effect according to levels of cardiovascular biomarkers at baseline
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02942407
|Principal Investigator:||Christopher Granger, MD||Duke University|
|Principal Investigator:||Glenn Chertow, MD||Stanford University|