Rationale and trial design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON)

Am J Nephrol. 2013;37(3):212-22. doi: 10.1159/000346948. Epub 2013 Feb 28.

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.

Conclusion: BEACON will be the first event-driven trial to evaluate the effect of an oral antioxidant and anti-inflammatory drug in advanced CKD.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use*
  • Clinical Trials Data Monitoring Committees
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / etiology
  • Double-Blind Method
  • Early Termination of Clinical Trials*
  • Glomerular Filtration Rate
  • Humans
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / therapeutic use
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / etiology
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Oleanolic Acid
  • methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate