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.
|Titolo:||Rationale and trial design of bardoxolone methyl evaluation in patients with chronic kidney disease and type 2 diabetes: The Occurrence of Renal Events (BEACON)|
|Parole Chiave:||Bardoxolone methyl; Cardiovascular death; Chronic kidney disease; Clinical trial; Diabetes mellitus; End-stage renal disease; Glomerular filtration rate; Nrf2; Trial design; Anti-Inflammatory Agents; Clinical Trials Data Monitoring Committees; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Double-Blind Method; Glomerular Filtration Rate; Humans; Oleanolic Acid; Renal Insufficiency, Chronic; Treatment Outcome; Early Termination of Clinical Trials; Nephrology|
|Settore Scientifico Disciplinare:||Settore MED/14 - Nefrologia|
|Data di pubblicazione:||apr-2013|
|Digital Object Identifier (DOI):||10.1159/000346948|
|Appare nelle tipologie:||01 - Articolo su periodico|