Mechanisms Contributing to Adverse Cardiovascular Events in Patients with Type 2 Diabetes Mellitus and Stage 4 Chronic Kidney Disease Treated with Bardoxolone Methyl
Melanie P Chin, Scott A Reisman, George L Bakris, Megan O'Grady, Peter G Linde, Peter A McCullough, David Packham, Nosratola D Vaziri, Keith W Ward, David G Warnock, Colin J Meyer
American Journal of Nephrology | KARGER | Published : 2014
BACKGROUND: Bardoxolone methyl, an Nrf2-activating and nuclear factor-κB-inhibiting semisynthetic oleanane triterpenoid compound, was evaluated in a phase 3 trial (BEACON) in patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD). The trial was terminated because of an increase in heart failure events in the bardoxolone methyl group, many of which appeared related to fluid retention. Thus, additional analyses were conducted to explain these serious adverse events. METHODS: Patients (n = 2,185) were randomized to receive once-daily bardoxolone methyl (20 mg) or placebo. Twenty-four-hour urine collections were analyzed in a subset of the BEACON population and fr..View full abstract
G.L.B., P.A.M., D.P., and N.D.V. have received honoraria from Reata Pharmaceuticals for their involvement with the BEACON trial. D.G.W. is a consultant to, and has an equity interest in Reata. M.P.C., S.A.R., M.O.G., K.W.W., and C.J.M. are employed by and/or have a financial interest in Reata. P.G.L. is employed by Abb Vie.