Once daily versus three times daily mesalazine granules in active ulcerative colitis: a double-blind, double-dummy, randomised, non-inferiority trial
- W Kruis1,
- G Kiudelis2,
- I Rácz3,
- I A Gorelov4,
- J Pokrotnieks5,
- M Horynski6,
- M Batovsky7,
- J Kykal8,
- S Boehm1,
- R Greinwald9,
- R Mueller9
- 1Evangelisches Krankenhaus Kalk, University of Cologne, Cologne, Germany
- 2Kaunas University of Medicine Hospital, Kaunas, Lithuania
- 3Petz Aladár County and Teaching Hospital, Győr, Hungary
- 4Central Medical–Sanitary Hospital #122, Moscow, Russia
- 5Latvian Gastroenterology Center – Paula Stradina University Hospital, Riga, Latvia
- 6Centrum Medyczne “SOPMED” NZOZ, Sopot, Poland
- 7Derer’s University Hospital, Bratislava, Slovak Republic
- 8Hospital Ricany, Ricany, Czech Republic
- 9Dr Falk Pharma GmbH, Freiburg, Germany
- Professor W Kruis, Evangelisches Krankenhaus Kalk, Buchforststr 2, D-51103, Cologne, Germany;
- Revised 26 July 2008
- Accepted 2 September 2008
- Published Online First 2 October 2008
Objectives: 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.
Design: A randomised, double-blind, double-dummy, parallel group, multicentre, international, phase III non-inferiority study.
Setting: 54 centres in 13 countries.
Patients: 380 patients with confirmed diagnosis of established or first attack of ulcerative colitis (clinical activity index (CAI)>4 and endoscopic index ⩾4 at baseline) were randomised and treated.
Interventions: 8-week treatment with either 3 g OD or 1 g TID mesalazine granules.
Main outcome measures: Clinical remission (CAI⩽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.
ClinicalTrials.gov Identifier: NCT00449722
A list of investigators of the International Salofalk OD Study Group is given in the appendix.
Funding: This study was funded in full by Dr Falk Pharma, Freiburg, Germany.
Competing interests: WK has served as a speaker and consultant for Dr Falk Pharma, Freiburg, Germany. RG and RM are employees of Dr Falk Pharma, Freiburg, Germany. All other authors have declared that they have no competing interests.
Ethics approval: This study was conducted in accordance with good clinical practice and the Declaration of Helsinki, and was approved by independent ethics committees for each centre, on 30 May 2005.