Late breaking oral abstracts– BEACON trial
Bardoxolone Methyl in Type 2 Diabetes and Stage 4 Chronic Kidney Disease
Glenn Chertow, MD—Stanford
The BEACON trial
Bardoxolone Methyl (BM) is most potent for known activators of Nrf2 pathway that help decrease oxidative stress. A stage 2 study had showed a decrease in crt in CKD in DMII.
AIM: Reduction of ESRD and cardiovascular death in CKD IV with this agent.
This was a Phase 3 randomized controlled trial, multi center. Stage IV stable ACEI/ ARB and some exclusion criteria including severe HTN and poorly controlled DMII.
Primary outcome was ESRD, and or cardiovascular death.
3 secondary outcomes: Change in eGFR, hospitalization for death and due to heart failure and composite heart and stroke risk.
Mean eGFR was 22.5 ml/min in both groups. Majority of patients had albuminuria. Many patients had retinopathy, neuropathy in both sides.
There were 70 outcomes in 69 patients in the BM group and 70 outcomes in 69 patients in placebo groups. No statistical difference in ESRD events and cardiovascular deaths. Secondary outcomes significant hazard with BM group. More heart failure in BM arm that was significant.
In conclusions, in DMII and CKD, BM did not reduce the risk of death and ESRD events. Significant cardiovascular events and CHF had to halt the trail in the BM side. Patient with hx of CHD and elevated BNP concentrations were at the highest risk.
Why??- Stage IV CKD and albuminuria are a high risk group for CV disease. BEAM trial was smaller and CKD was more advanced. Why so prominent here and not in BEAM is unclear per Dr. Chertow.
Number of lessons to be learned: CAUTION is always wise. In high risk population, vigilance might be needed in early phases of clinical trials. We need to explore new and innovative ways to prevent ESRD. A good start nevertheless.
Post written by Dr. Kenar Jhaveri, eAJKD Editor.