Bardoxolone Methyl in Type 2 Diabetes and Stage 4 Chronic Kidney Disease
By D. de Zeeuw, T. Akizawa, P. Audhya, G. Bakris, M. Chin, H. Christ-schmidt, A. Goldsberry, M. Houser, Melissa Krauth, H. L. Lambers Heerspink and 10 more. New England Journal of Medicine, 2013
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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 ClinicalTrials.gov number, NCT01351675.)
Subfields: Cardiology and Cardiovascular Medicine, Nephrology, Physiology
View Paper: https://www.semanticscholar.org/paper/33ac0517c8ef6d050673172abd0613d2df56c9d2
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Citations in the corpus
- Kidney fibrosis: from mechanisms to therapeutic medicines (2023, background): “However, in a larger phase 3 trial including more than 2000 patients with stage 4 CKD and diabetes (BEACON study), bardoxolone methyl failed to reduce the risk of ESRD or death from cardiovascular causes, along with an increased rate of cardiovascular events.(259) Researchers conducted post-hoc anal”
- Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment (2021, result): “The BEACON study also demonstrated the results of bardoxolone methyl inducing an increase in GFR, but this study was discontinued, for safety reasons related to heart failure due to fluid retention [196, 197].”
- The Impact of Oxidative Stress and Inflammation on RPE Degeneration in Non-neovascular AMD (2017, background): “…Nrf2, was halted in a phase III trial that tested whether it reduced the risk of end-stage renal disease (ESRD) or death from cardiovascular causes among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease because of unacceptable adverse effects (de Zeeuw et al., 2013).”