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Type: Journal article
Title: Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease
Author: De Zeeuw, D.
Akizawa, T.
Audhya, P.
Bakris, G.
Chin, M.
Christ-Schmidt, H.
Goldsberry, A.
Houser, M.
Krauth, M.
Lambers Heerspink, H.
McMurray, J.
Meyer, C.
Parving, H.
Remuzzi, G.
Toto, R.
Vaziri, N.
Wanner, C.
Wittes, J.
Wrolstad, D.
Chertow, G.
et al.
Citation: New England Journal of Medicine, 2013; 369(26):2492-2503
Publisher: Massachusetts Medical Society
Issue Date: 2013
ISSN: 0028-4793
Statement of
Dick de Zeeuw, Tadao Akizawa, Paul Audhya, George L. Bakris, Melanie Chin ... Gary A. Wittert ... et al.
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 m2 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 number, NCT01351675.)
Keywords: BEACON Trial Investigators; Humans; Diabetic Nephropathies; Kidney Failure, Chronic; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Weight Loss; Oleanolic Acid; Glomerular Filtration Rate; Treatment Failure; Double-Blind Method; Aged; Middle Aged; Female; Male; NF-E2-Related Factor 2; Renal Insufficiency, Chronic; Intention to Treat Analysis; Kaplan-Meier Estimate
Rights: © 2013, Massachusetts Medical Society
RMID: 0030075902
DOI: 10.1056/NEJMoa1306033
Appears in Collections:Medicine publications

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