title: Cyclosporine C2 monitoring for the treatment of frequently relapsing nephrotic syndrome in children: a multicenter randomized phase II trial.
abstract: OBJECTIVE
  An open-label, multicenter, randomized phase II trial was conducted from July 1, 2005 to March 29, 2011 to compare two protocols for treating children with frequently relapsing nephrotic syndrome using microemulsified cyclosporine.
  
  
  METHODS
  Ninety-three children with frequently relapsing nephrotic syndrome were randomly assigned to group A (n=46) or group B (n=47). In both groups, the 2-hour postdose cyclosporine level was monitored. For group A, the cyclosporine target was set to 600-700 ng/ml for the first 6 months and 450-550 ng/ml for the next 18 months; for group B, it was set to 450-550 ng/ml for the first 6 months and 300-400 ng/ml for the next 18 months. The primary end point was the sustained remission rate. At the end of the study, if there was no difference in safety profile between the two groups and the sustained remission rate in group A was superior to group B with a decision threshold of 8%, then the regimen for group A would be determined the better treatment.
  
  
  RESULTS
  Eight children from an ineligible institution, where cyclosporine levels were not measured, were excluded from all analyses. At 24 months, the sustained remission rate was nonsignificantly higher in group A (n=43) than group B (n=42; 64.4% versus 50.0%; hazard ratio, 0.57; 95% confidence interval, 0.29 to 1.11; P=0.09), and the progression-free survival rate was significantly higher (88.1% versus 68.4%; hazard ratio, 0.33; 95% confidence interval, 0.12 to 0.94; P=0.03). The relapse rate was significantly lower in group A than group B (0.41 versus 0.95 times/person-year; hazard ratio, 0.43; 95% confidence interval, 0.19 to 0.84; P=0.02). The rate and severity of adverse events were similar in both treatment groups.
  
  
  CONCLUSIONS
  The sustained remission rate was not significantly different between the two treatment groups, but the regimen with the higher 2-hour postdose cyclosporine level target improved progression-free survival and reduced the relapse rate.
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sako
authors.forename: Mari Saito
authors.initials: MS
authors.lastname: Oba
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hataya
authors.forename: Ryojiro
authors.initials: R
authors.lastname: Tanaka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ohwada
authors.forename: Koichi
authors.initials: K
authors.lastname: Kamei
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishikura
authors.forename: Nahoko
authors.initials: N
authors.lastname: Yata
authors.forename: Kandai
authors.initials: K
authors.lastname: Nozu
authors.forename: Masataka
authors.initials: M
authors.lastname: Honda
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Michio
authors.initials: M
authors.lastname: Nagata
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Norishige
authors.initials: N
authors.lastname: Yoshikawa
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D001711:Biotransformation; D002626:Chemistry, Pharmaceutical; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003524:Cyclosporins / Q000097:blood / Q000493:pharmacokinetics*; D018572:Disease-Free Survival; D016903:Drug Monitoring / Q000379:methods*; D004655:Emulsions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007223:Infant; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D009404:Nephrotic Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D003524:Cyclosporins; D004655:Emulsions; D007166:Immunosuppressive Agents; C100000:cyclosporin C; D016572:Cyclosporine