BACKGROUND:Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic triterpenoid that reduces oxidative stress and inflammation through Nrf2 activation and inhibition of NF-κB was previously shown to increase estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes mellitus. To date, no antioxidant or anti-inflammatory therapy has proved successful at slowing the progression of CKD. METHODS: Herein, we describe the design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON) trial, a multinational, multicenter, double-blind, randomized, placebo-controlled Phase 3 trial designed to determine whether long-term administration of bardoxolone methyl (on a background of standard therapy, including RAAS inhibitors) safely reduces renal and cardiac morbidity and mortality. RESULTS: The primary composite endpoint is time-to-first occurrence of either end-stage renal disease or cardiovascular death. Secondary endpoints include the change in eGFR and time to occurrence of cardiovascular events. CONCLUSION: BEACON will be the first event-driven trial to evaluate the effect of an oral antioxidant and anti-inflammatory drug in advanced CKD.
RCT Entities:
BACKGROUND:Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic triterpenoid that reduces oxidative stress and inflammation through Nrf2 activation and inhibition of NF-κB was previously shown to increase estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes mellitus. To date, no antioxidant or anti-inflammatory therapy has proved successful at slowing the progression of CKD. METHODS: Herein, we describe the design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON) trial, a multinational, multicenter, double-blind, randomized, placebo-controlled Phase 3 trial designed to determine whether long-term administration of bardoxolone methyl (on a background of standard therapy, including RAAS inhibitors) safely reduces renal and cardiac morbidity and mortality. RESULTS: The primary composite endpoint is time-to-first occurrence of either end-stage renal disease or cardiovascular death. Secondary endpoints include the change in eGFR and time to occurrence of cardiovascular events. CONCLUSION:BEACON will be the first event-driven trial to evaluate the effect of an oral antioxidant and anti-inflammatory drug in advanced CKD.
Authors: Dick de Zeeuw; Tadao Akizawa; Paul Audhya; George L Bakris; Melanie Chin; Heidi Christ-Schmidt; Angie Goldsberry; Mark Houser; Melissa Krauth; Hiddo J Lambers Heerspink; John J McMurray; Colin J Meyer; Hans-Henrik Parving; Giuseppe Remuzzi; Robert D Toto; Nosratola D Vaziri; Christoph Wanner; Janet Wittes; Danielle Wrolstad; Glenn M Chertow Journal: N Engl J Med Date: 2013-11-09 Impact factor: 91.245
Authors: Melanie P Chin; George L Bakris; Geoffrey A Block; Glenn M Chertow; Angie Goldsberry; Lesley A Inker; Hiddo J L Heerspink; Megan O'Grady; Pablo E Pergola; Christoph Wanner; David G Warnock; Colin J Meyer Journal: Am J Nephrol Date: 2018-01-18 Impact factor: 3.754
Authors: Dana V Rizk; Arnold L Silva; Pablo E Pergola; Robert Toto; David G Warnock; Melanie P Chin; Angie Goldsberry; Megan O'Grady; Colin J Meyer; Peter A McCullough Journal: Cardiorenal Med Date: 2019-06-06 Impact factor: 2.041
Authors: Eugene J Barrett; Zhenqi Liu; Mogher Khamaisi; George L King; Ronald Klein; Barbara E K Klein; Timothy M Hughes; Suzanne Craft; Barry I Freedman; Donald W Bowden; Aaron I Vinik; Carolina M Casellini Journal: J Clin Endocrinol Metab Date: 2017-12-01 Impact factor: 5.958