title: 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: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  ClinicalTrials.gov NCT00500682 ; NCT00501046 .
authors.affiliation: Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Schulman
authors.affiliation: University of Colorado Health Sciences Center, Denver, CO, USA.
authors.forename: Tomas
authors.initials: T
authors.lastname: Berl
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Beck
authors.affiliation: Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.|IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.|Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.affiliation: University of Heidelberg, Heidelberg, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Kureha Corporation, 3-26-2, Hyakunin-cho, Shinjuku-ku, Tokyo, 169-8503, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shobu
authors.affiliation: Kureha Corporation, 3-26-2, Hyakunin-cho, Shinjuku-ku, Tokyo, 169-8503, Japan. mami-k@kureha.co.jp.
authors.forename: Mami
authors.initials: M
authors.lastname: Kikuchi
mesh_terms: D000368:Aged; D002244:Carbon / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000627:therapeutic use*; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy* / Q000628:therapy; D014481:United States
chemical_list: D010087:Oxides; D002244:Carbon; C040896:AST 120; D003404:Creatinine
keywords: AST-120; Chronic kidney disease; Clinical trial; Spherical carbon adsorbent; Uremic toxin