The following is a summary of “VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of Chronic Kidney Disease in Patients with Metabolic Acidosis,” published in the January 2024 issue of Nephrology by Tangri et al.
Researchers started a retrospective study to investigate whether veverimer, a bicarbonate-elevating gastrointestinal acid binder, could slow the progression of chronic kidney disease (CKD) in metabolic acidosis patients.
They conducted a phase 3, double-blind, placebo-controlled trial involving CKD patients (estimated glomerular filtration rate [eGFR] 20-40 mL/min/1.73 m 2) with metabolic acidosis (serum bicarbonate 12-20 mEq/L) from 35 countries. Randomizing to veverimer or placebo, the primary outcome was CKD progression—defined as end-stage kidney disease (transplantation or dialysis), sustained eGFR decline >40%, or death due to kidney failure.
The results showed baseline eGFR of 29.2 ± 6.3 mL/min/1.73 m 2 and serum bicarbonate of 17.5±1.4 mEq/L. After the active-treatment run-in, serum bicarbonate increased to 23.4 ± 2.0 mEq/L. Following randomized withdrawal, mean serum bicarbonate was 22.0 ± 3.0 mEq/L and 20.9 ± 3.3 mEq/L in veverimer and placebo groups at Month 3, maintaining a stable ∼1 mEq/L difference for the first 24 months. There was no difference in primary endpoint events between the veverimer and placebo groups 149/741 vs 148/739 (HR, 0.99; 95% CI, 0.8 to 1.2; P=0.90). The incidence of severe and overall adverse events did not differ between the groups.
They concluded that veverimer failed to show any benefit in slowing CKD progression in patients with metabolic acidosis, potentially due to insufficient bicarbonate level improvement.
Source: journals.lww.com/jasn/abstract/9900/valor_ckd__a_multicenter,_randomized,_double_blind.234.aspx
