title: Rationale and trial design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON).
abstract: 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.
  
  
  CONCLUSIONS
  BEACON will be the first event-driven trial to evaluate the effect of an oral antioxidant and anti-inflammatory drug in advanced CKD.
authors: Department of Clinical Pharmacology, University of Groningen, University Medical Center, Groningen, The Netherlands. d.de.zeeuw@umcg.nl
authors: Dick
authors: D
authors: de Zeeuw
authors: Tadao
authors: T
authors: Akizawa
authors: Rajiv
authors: R
authors: Agarwal
authors: Paul
authors: P
authors: Audhya
authors: George L
authors: GL
authors: Bakris
authors: Melanie
authors: M
authors: Chin
authors: Melissa
authors: M
authors: Krauth
authors: Hiddo J
authors: HJ
authors: Lambers Heerspink
authors: Colin J
authors: CJ
authors: Meyer
authors: John J
authors: JJ
authors: McMurray
authors: Hans-Henrik
authors: HH
authors: Parving
authors: Pablo E
authors: PE
authors: Pergola
authors: Giuseppe
authors: G
authors: Remuzzi
authors: Robert D
authors: RD
authors: Toto
authors: Nosratola D
authors: ND
authors: Vaziri
authors: Christoph
authors: C
authors: Wanner
authors: David G
authors: DG
authors: Warnock
authors: Janet
authors: J
authors: Wittes
authors: Glenn M
authors: GM
authors: Chertow
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D026661:Clinical Trials Data Monitoring Committees; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D005919:Glomerular Filtration Rate; D006801:Humans; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D009828:Oleanolic Acid; C445068:bardoxolone methyl