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Bardoxolone Methyl in Type 2 Diabetes and Stage 4 Chronic Kidney Disease
Journal article   Open access   Peer reviewed

Bardoxolone Methyl in Type 2 Diabetes and Stage 4 Chronic Kidney Disease

Dick de Zeeuw, Tadao Akizawa, Paul Audhya, George L. Bakris, Melanie Chin, Heidi Christ-Schmidt, Angie Goldsberry, Mark Houser, Melissa Krauth, Hiddo J. Lambers Heerspink, …
The New England journal of medicine, Vol.369(26), pp.2492-2503
12/26/2013
DOI: 10.1056/NEJMoa1306033
PMCID: PMC4496027
PMID: 24206459
url
https://doi.org/10.1056/NEJMoa1306033View
Published (Version of record) Open Access

Abstract

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 to <30 ml per minute per 1.73 m(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<0.001). Estimated GFR, blood pressure, and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group, as compared with the placebo group. 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.)
 General & Internal Medicine Life Sciences & Biomedicine Medicine, General & Internal Science & Technology

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