The effects of AST-120 on chronic kidney disease progression in the United States of America: a post hoc subgroup analysis of randomized controlled trials

Abstract

Background: The orally administered spherical carbon adsorbent AST-120 is used on-label in Asian countries to slow renal disease progression in patients with progressive chronic kidney disease (CKD). Recently, two multinational, randomized, double-blind, placebo-controlled, phase 3 trials (Evaluating Prevention of Progression in Chronic Kidney Disease [EPPIC] trials) examined AST-120's efficacy in slowing CKD progression. This study assessed the efficacy of AST-120 in the subgroup of patients from the United States of America (USA) in the EPPIC trials.

Methods: In the EPPIC trials, 2035 patients with moderate to severe CKD were studied, of which 583 were from the USA. The patients were randomly assigned to two groups of equal size that were treated with AST-120 or placebo (9 g/day). The primary end point was a composite of dialysis initiation, kidney transplantation, or serum creatinine doubling.

Results: The Kaplan-Meier curve for the time to achieve the primary end point in the placebo-treated patients from the USA was similar to that projected before the study. The per protocol subgroup analysis of the population from the USA which included patients with compliance rates of ≥67 % revealed a significant difference between the treatment groups in the time to achieve the primary end point (Hazard Ratio, 0.74; 95 % Confidence Interval, 0.56-0.97).

Conclusions: This post hoc subgroup analysis of EPPIC study data suggests that treatment with AST-120 might delay the time to primary end point in CKD patients from the USA. A further randomized controlled trial in progressive CKD patients in the USA is necessary to confirm the beneficial effect of adding AST-120 to standard therapy regimens.

Trial registration: ClinicalTrials.gov NCT00500682 ; NCT00501046 .

Keywords: AST-120; Chronic kidney disease; Clinical trial; Spherical carbon adsorbent; Uremic toxin.

Figures

Fig. 1

Kaplan-Meier plots of primary end point achievement in placebo-treated USA and outside USA populations. CI confidence interval, HR hazard ratio

Fig. 2

Achievement of primary and secondary end points in the EPPIC-USA subpopulation. a Sensitivity analyses of the primary efficacy end point were performed to evaluate the robustness of the results to censoring patterns. b First occurrence of dialysis, kidney transplantation, or doubling of sCr in the 84 days after the last sCr assessment or last dose. Patients who did not have an event in this period were censored at the last sCr assessment. CKD chronic kidney disease, DN diabetic nephropathy, ESRD end stage renal disease, HR hazard ratio, ITT intent-to-treat, PP per protocol, sCr serum creatinine

Fig. 3

Kaplan-Meier plots of primary end point achievement in the EPPIC-USA population. a ITT primary end point censored at last contact, b PP primary end point censored at last contact, c PP ESRD censored at last contact, d ITT DN primary end point censored at last contact, e PP DN primary end point censored at last contact, f PP DN ESRD censored at last contact. DN diabetic nephropathy, ESRD end stage renal disease, ITT intent-to-treat, PP per protocol

Fig. 4

Achievement of primary end points in the EPPIC-USA subgroups. ACEI angiotensin converting enzyme inhibitor, ARB angiotensin receptor blocker, CKD chronic kidney disease, CRP C-reactive protein, eGFR estimated glomerular filtration rate, sCr serum creatinine, UP/UCr Urinary total protein to urinary creatinine ratio