High Impact Clinical Trials: Bardoxolone in type 2 diabetics with CKD stage 4 — BEACON Trial

Speaker: Glenn Chertow
[twitter transcript]

Coming off the positive results of the BEAM trial (link), the BEACON trial yielded significantly disappointing results. As a quick review: bardoxolone is a potent activator of NRF2. NRF2 decreases NFkB production, which in turn decreases oxidative stress. It is believed that oxidative stress is the main cause of kidney injury. After the successful results of the phase 2 BEAM trial, BEACON was undertaken to see its effects on the onset of ESRD and CV death (these were the primary endpoints).

Alas, there was no difference in either of the primary endpoints between the bardoxolone and placebo groups. While this could be explained away by faulty trial design (e.g., too short a follow up), the trial was actually terminated early for safety concerns. There was a greater percentage of side effects in the bardoxolone group, namely increased deaths, than the placebo group.

The audience seemed to be very appreciative of the authors for having conducted this study, pleased with the NEJM for publishing a negative study, but overall bummed at another negative clinical trial in nephrology.