May 12, 2017 – The Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation (RENAL-AF) trial is the first randomized clinical trial of any anticoagulant in patients on hemodialysis with atrial fibrillation (AF).
RENAL-AF is an interventional, prospective, open-label, blinded end-point evaluation trial that has recently enrolled its first patients with AF and end-stage renal disease (ESRD) receiving hemodialysis. Led by the DCRI’s Christopher Granger, MD, (pictured left) and Stanford University’s Glenn M. Chertow, MD, the study will assess the safety and efficacy of the oral anticoagulant apixaban by randomizing patients to apixaban versus warfarin, with clinically relevant, non-major bleeding event as the primary outcome.
“Roughly 20 per cent of patients that are on hemodialysis have a high burden of AF, yet there have been no studies or randomized trials addressing the use of oral anticoagulants in this population for AF and stroke prevention,” said Granger, principal investigator of the trial. Compared to the general population, AF is far more common and associated with a much higher risk of stroke in the dialysis population, leaving a major unmet clinical need in this high-risk population.
Warfarin has long been the anticoagulant of choice for preventing stroke in patients with AF. However, warfarin requires regular blood tests and can be affected by other medications and foods. These concerns are particularly important for patients on hemodialysis since they often have irregular diets and multiple medication changes. Newer blood thinners such as apixaban have been proven to be safer than warfarin in the general population but they have never been tested in patients on hemodialysis.
“All novel oral anticoagulants are cleared by the kidneys, however, apixaban has less renal clearance than the others, making it an ideal medication to study in this population,” said the DCRI’s Sean Pokorney, MD (pictured right).
The primary outcome assessed in the RENAL-AF trial is the time from randomization to the first major or clinically relevant non-major bleeding event, a common safety concern for any anticoagulant. Adherence to treatment with apixaban or warfarin will be assessed through medication adherence questionnaires, as well as pill counts for patients randomized to apixaban and time spent in therapeutic range for warfarin (which is assessed by routine blood checks). The study is expected to enroll over 750 adult patients across the United States. The full study will conclude by mid-2020.
The researchers are also conducting a pharmacokinetic and pharmacodynamic study within the RENAL-AF trial of patients randomized to apixaban. Biomarker samples are also being collected at baseline for research related to bleeding and stroke events.
“The first 50 patients will have extensive testing to understand how apixaban is absorbed and metabolized in patients with ESRD and AF,” Pokorney said. “These will be the first data to come out of the RENAL-AF trial, which means we will have some very important results as early as the end of this year.”
“Since this is the very first randomized clinical trial of any anticoagulant in patients on hemodialysis with AF, whatever the results show us, it will be important,” Granger said. “It will be an advance for clinical medicine if apixaban turns out to be safe and effective for this important population.”