title: Once daily versus three times daily mesalazine granules in active ulcerative colitis: a double-blind, double-dummy, randomised, non-inferiority trial.
abstract: OBJECTIVE
  To determine the therapeutic equivalence and safety of once daily (OD) versus three times daily (TID) dosing of a total daily dose of 3 g Salofalk (mesalazine) granules in patients with active ulcerative colitis.
  
  
  METHODS
  A randomised, double-blind, double-dummy, parallel group, multicentre, international, phase III non-inferiority study.
  
  
  METHODS
  54 centres in 13 countries.
  
  
  METHODS
  380 patients with confirmed diagnosis of established or first attack of ulcerative colitis (clinical activity index (CAI)>4 and endoscopic index > or =4 at baseline) were randomised and treated.
  
  
  METHODS
  8-week treatment with either 3 g OD or 1 g TID mesalazine granules.
  
  
  METHODS
  Clinical remission (CAI< or =4) at study end.
  
  
  RESULTS
  380 patients were evaluable for efficacy and safety by intention-to-treat (ITT); 345 for per protocol (PP) analysis. In the ITT population, 79.1% in the OD group (n = 191) and 75.7% in the TID group (n = 189) achieved clinical remission (p<0.0001 for non-inferiority). Significantly more patients with proctosigmoiditis achieved clinical remission in the OD group (86%; n = 97) versus the TID group (73%; n = 100; p = 0.0298). About 70% of patients in both treatment groups achieved endoscopic remission, and 35% in the OD group and 41% in the TID group achieved histological remission. About 80% of all patients preferred OD dosing. Similar numbers of adverse events occurred in 55 patients (28.8%) in the OD group and in 61 patients (32.3%) in the TID group, indicating that the two dosing regimens were equally safe and well tolerated.
  
  
  CONCLUSIONS
  OD 3 g mesalazine granules are as effective and safe as a TID 1 g schedule. With respect to the best possible adherence of patients to the treatment, OD dosing of mesalazine should be the preferred application mode in active ulcerative colitis.
authors.affiliation: Evangelisches Krankenhaus Kalk, University of Cologne, Cologne, Germany. sallhoff@evkk.de
authors.forename: W
authors.initials: W
authors.lastname: Kruis
authors.forename: G
authors.initials: G
authors.lastname: Kiudelis
authors.forename: I
authors.initials: I
authors.lastname: Rácz
authors.forename: I A
authors.initials: IA
authors.lastname: Gorelov
authors.forename: J
authors.initials: J
authors.lastname: Pokrotnieks
authors.forename: M
authors.initials: M
authors.lastname: Horynski
authors.forename: M
authors.initials: M
authors.lastname: Batovsky
authors.forename: J
authors.initials: J
authors.lastname: Kykal
authors.forename: S
authors.initials: S
authors.lastname: Boehm
authors.forename: R
authors.initials: R
authors.lastname: Greinwald
authors.forename: R
authors.initials: R
authors.lastname: Mueller
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000627:therapeutic use; D016009:Chi-Square Distribution; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D003113:Colonoscopy; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D010349:Patient Compliance; D018401:Sample Size; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine