Clinical trial NCT00746447: Once Daily (OD) Versus Three Times Daily (TID) Dosing With Mesalazine Granules for Prevention of Recurrence of Ulcerative Colitis (UC)
Official title: Double-blind, Double-dummy, Randomised, Multicentre, 12-months, Comparative Study of the Efficacy and Tolerability of Once Daily 3.0 g Mesalazine Granules vs. Once Daily 1.5 g Mesalazine Granules vs. Three Times Daily 0.5 g Mesalazine Granules for Maintenance of Remission in Patients With Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colitis, Ulcerative
Recurrence
Keywords: maintenance
5-ASA
mesalamine
mesalazine
ulcerative colitis
Lead sponsor: Dr. Falk Pharma GmbH
Sponsor class: INDUSTRY
First posted: 2008-09-04
Enrollment: 648
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study intends to study the efficacy and tolerability of once daily 3.0 g mesalazine granules vs. once daily 1.5 g mesalazine granules vs. three times daily 0.5 g mesalazine granules for maintenance of remission in patients with ulcerative colitis


Eligibility criteria: Inclusion Criteria:

* Signed informed consent,
* Men or women aged 18 to 75 years,
* Historically confirmed diagnosis of ulcerative colitis by endoscopy and histology,
* Patient being in remission, defined (according to Rachmilewitz) as:

Clinical Activity Index (CAI) \<= 4, and Endoscopic Index (EI) \< 4,

* Extent of inflammation during last acute episode was \>15 cm beyond the anal margin,
* Last acute episode ended within 3 months prior to study entry.

Exclusion Criteria:

* Crohn's disease,
* Prior bowel resection leading to diarrhoea,
* Toxic megacolon,
* Gastric or duodenal ulcer,
* Haemorrhagic diathesis,
* Presence of symptomatic organic disease of the gastrointestinal tract (with the exception of haemorrhoids or hiatal hernia),
* Active colorectal cancer or a history of colorectal cancer,
* Serious other secondary illnesses of an acute or chronic nature,
* Asthma,
* Severe impairment of renal (e.g., serum creatinine \> 1.5 mg/dl) and/or liver functions (e.g., serum transaminase \[ALT and/or AST\] or alkaline phosphatase \>=2x upper limit of normal \[ULN\]),
* Application of immunosuppressants within 3 months and/or corticosteroids (oral, intravenous \[IV\] or topical rectal) within 30 days prior to baseline,
* Application of non-steroidal anti-inflammatory drugs (NSAIDs) as long term treatment (i.e. \> 6 weeks), other than acetylsalicylic acid (\<= 350 mg/day), or paracetamol,
* Known intolerance/hypersensitivity to salicylic acid and its derivatives or to any of the other constituents of the study drugs,
* Well-founded doubt about the patient's cooperation,
* Existing or intended pregnancy, breast-feeding,
* Women of child-bearing potential without adequate contraceptive protection, e.g., hormonal contraception, intrauterine device (IUD), double-barrier method of contraception (e.g., use of a condom and spermicide), partner has undergone vasectomy and subject is in monogamous relationship. The investigator is responsible for determining whether the subject has adequate birth control for study participation,
* Participation in another clinical trial within the last 30 days,simultaneous participation in another clinical trial, or previous participation in this trial.

Primary outcomes:
measure: Percentage of patients still in clinical remission at the final/withdrawal examination, with clinical relapse defined as a CAI >4 with an increase of ≥3 points from baseline.
timeFrame: week 52 or premature withdrawal
Secondary outcomes:
measure: Time to relapse
timeFrame: within 52 weeks
measure: Proportion of patients in endoscopical remission, defined as a mucosal appearance score of ≤ 1 at final/withdrawal examination.
timeFrame: week 52 or premature withdrawal
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: Evangelisches Krankenhaus Kalk, Medical Dept.
Study officials:
affiliation: Dr. Falk Pharma GmbH
name: Ralph Mueller, Dr.
role: STUDY_DIRECTOR
References:
citation: Kruis W, Jonaitis L, Pokrotnieks J, Mikhailova TL, Horynski M, Batovsky M, Lozynsky YS, Zakharash Y, Racz I, Kull K, Vcev A, Faszczyk M, Dilger K, Greinwald R, Mueller R; International Salofalk OD Study Group. Randomised clinical trial: a comparative dose-finding study of three arms of dual release mesalazine for maintaining remission in ulcerative colitis. Aliment Pharmacol Ther. 2011 Feb;33(3):313-22. doi: 10.1111/j.1365-2036.2010.04537.x. Epub 2010 Dec 8.