Tangri, Navdeep;
Mathur, Vandana S;
Bushinsky, David A;
Klaerner, Gerrit;
Li, Elizabeth;
Parsell, Dawn;
Stasiv, Yuri;
... Inker, Lesley A; + view all
(2024)
VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of Chronic Kidney Disease in Patients with Metabolic Acidosis.
Journal of the American Society of Nephrology
10.1681/ASN.0000000000000292.
(In press).
![[thumbnail of VALOR CKD.pdf]](https://discovery.ucl.ac.uk/style/images/fileicons/text.png) |
Text
VALOR CKD.pdf - Accepted Version Access restricted to UCL open access staff until 24 January 2025. Download (951kB) |
Abstract
BACKGROUND: Metabolic acidosis is common in chronic kidney disease (CKD), but whether its treatment slows CKD progression is unknown. Veverimer, a novel hydrochloric acid binder that removes acid from the gastrointestinal tract, leads to an increase in serum bicarbonate. METHODS: In a Phase 3, double-blind, placebo-controlled trial, patients with CKD (estimated glomerular filtration rate [eGFR] of 20-40 mL/min/1.73 m2) and metabolic acidosis (serum bicarbonate of 12-20 mEq/L) from 35 countries were randomized to veverimer or placebo. The primary outcome was the composite endpoint of CKD progression, defined as the development of end-stage kidney disease (kidney transplantation or maintenance dialysis), a sustained decline in eGFR of >40% from baseline, or death due to kidney failure. RESULTS: The mean (±SD) baseline eGFR was 29.2 ± 6.3 mL/min/1.73 m2 and serum bicarbonate was 17.5±1.4 mEq/L; this increased to 23.4 ± 2.0 mEq/L after the active-treatment run-in. Following randomized withdrawal, the mean serum bicarbonate was 22.0 ± 3.0 mEq/L and 20.9 ± 3.3 mEq/L in the veverimer and placebo groups at Month 3 and this ∼ 1mEq/L difference remained stable for the first 24 months. A primary endpoint event occurred in 149/741 and 148/739 patients in the veverimer and placebo groups, respectively (hazard ratio, 0.99; 95 % CI, 0.8 to 1.2; P=0.90). Serious and overall adverse event incidence did not differ between the groups. CONCLUSIONS: Among patients with CKD and metabolic acidosis, treatment with veverimer did not slow CKD progression. The lower than expected bicarbonate separation may have hindered the ability to test the hypothesis. (Funded by Tricida, Inc.; VALOR-CKD ClinicalTrials.gov number, NCT037102).
Archive Staff Only
 |
View Item |
