Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease.
BACKGROUND: Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown.
METHODS: We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate [GFR], 15 tom(2) of body-surface area) to bardoxolone methyl, at a daily dose of 20 mg, or placebo. The primary composite outcome was end-stage renal disease (ESRD) or death from cardiovascular causes.
RESULTS: The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee; the median follow-up was 9 months. A total of 69 of 1088 patients (6%) randomly assigned to bardoxolone methyl and 69 of 1097 (6%) randomly assigned to placebo had a primary composite outcome (hazard ratio in the bardoxolone methyl group vs. the placebo group, 0.98; 95% confidence interval [CI], 0.70 to 1.37; P=0.92). In the bardoxolone methyl group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes. A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure, as compared with 55 in the placebo group (hazard ratio, 1.83; 95% CI, 1.32 to 2.55; P
CONCLUSIONS: Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes. A higher rate of cardiovascular events with bardoxolone methyl than with placebo prompted termination of the trial. (Funded by Reata Pharmaceuticals; BEACON ClinicalTrials.gov number, NCT01351675.).
Published In/Presented At
de Zeeuw, D., Akizawa, T., Audhya, P., Bakris, G. L., Chin, M., Christ-Schmidt, H., Goldsberry, A., Houser, M., Krauth, M., Lambers Heerspink, H. J., McMurray, J. J., Meyer, C. J., Parving, H. H., Remuzzi, G., Toto, R. D., Vaziri, N. D., Wanner, C., Wittes, J., Wrolstad, D., Chertow, G. M., … BEACON Trial Investigators (2013). Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. The New England journal of medicine, 369(26), 2492–2503. https://doi.org/10.1056/NEJMoa1306033
Medicine and Health Sciences
Department of Medicine