Diabetic kidney disease BEACON extinguished
medwireNews: The BEACON trial of the synthetic triterpenoid bardoxolone methyl was halted prematurely due to safety concerns, shows research published in the New England Journal of Medicine.
Treatment failed to prevent Type 2 diabetes patients with stage 4 chronic kidney disease (CKD) from progressing to end-stage renal disease (ESRD) or dying from cardiovascular causes, with 6% of both the 1088 patients given bardoxolone methyl 20 mg/day and the 1087 patients given placebo reaching this composite endpoint.
While the researchers say “too few events occurred during the trial to determine the true effect of the drug,” the study was terminated because of a significantly higher incidence of hospitalization for heart failure or death from heart failure in the patients given the drug compared with those given placebo (96 vs 55, hazard ratio [HR]=1.83).
And significantly more patients given bardoxolone methyl than placebo reached the composite endpoint of nonfatal myocardial infarction or stroke, hospitalization for heart failure, or death from cardiovascular causes (139 vs 86, HR=1.71).
Bardoxolone methyl was also associated with a significantly higher rate of any serious adverse events than placebo (33 vs 27%), including albuminuria and elevated heart rate, as well as a significant decrease in body weight and a significant increase in mean diastolic blood pressure from baseline compared with placebo.
“The mechanism linking bardoxolone methyl to heart failure is unknown,” say Glenn Chertow (Stanford University, Alto, California, USA) and fellow BEACON (Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus: the Occurrence of Renal Events) investigators.
“Since an excess in heart-failure events was unanticipated, echocardiography was not performed routinely before randomization.”
Nevertheless, they suggest that increasing fluid retention, heart rate and blood pressure may have combined to induce heart failure in patients at particular risk for the disease and say it is possible that bardoxolone methyl activation of the transcription factor Nrf2 may have “rendered this particular population vulnerable.”
medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013
By Lynda Williams, Senior medwireNews Reporter