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

Gerald Schulman, Tomas Berl, Gerald J. Beck, Giuseppe Remuzzi, Eberhard Ritz, Miho Shimizu, Yuko Shobu, Mami Kikuchi

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalBMC Nephrology
Volume17
Issue number1
DOIs
Publication statusPublished - Sep 30 2016

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Chronic Renal Insufficiency
Disease Progression
Randomized Controlled Trials
Placebos
AST 120
Patient Compliance
Kidney Transplantation
Dialysis
Creatinine
Therapeutics
Carbon
Confidence Intervals
Kidney
Serum
Population

Keywords

  • AST-120
  • Chronic kidney disease
  • Clinical trial
  • Spherical carbon adsorbent
  • Uremic toxin

ASJC Scopus subject areas

  • Nephrology

Cite this

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. / Schulman, Gerald; Berl, Tomas; Beck, Gerald J.; Remuzzi, Giuseppe; Ritz, Eberhard; Shimizu, Miho; Shobu, Yuko; Kikuchi, Mami.

In: BMC Nephrology, Vol. 17, No. 1, 30.09.2016, p. 1-8.

Research output: Contribution to journalArticle

Schulman, Gerald ; Berl, Tomas ; Beck, Gerald J. ; Remuzzi, Giuseppe ; Ritz, Eberhard ; Shimizu, Miho ; Shobu, Yuko ; Kikuchi, Mami. / 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. In: BMC Nephrology. 2016 ; Vol. 17, No. 1. pp. 1-8.
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AB - 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.

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