Once Versus Twice Daily Mesalamine to Induce Remission in Pediatric Ulcerative Colitis
Condition: Mild to Moderate Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to evaluate effectiveness of once daily dosing of Pentasa
      compared with twice daily in children with mild to moderate active ulcerative colitis.
    

Detailed description: 
      Several randomized controlled trials (RCTs) have affirmed the efficacy of 5-aminosalicylic
      acid (5-ASA) and sulfasalazine in the acute treatment of mild to moderate exacerbations, as
      well as in the maintenance of clinical remission. Initially, common practice was to prescribe
      5-ASA in three divided doses. Slow release once daily mesalamine with Multi Matrix System
      (MMX) technology was shown to be effective in induction and maintenance of remission of adult
      ulcerative colitis (UC). Since transit time of the colon is much slower than the small-bowel,
      and since the active ingredient should act locally on the colon, less frequent dosing of the
      regular formulation may also provide sufficient colonic coverage. Indeed, two recent studies
      among adults with UC suggest that once daily dosing of mesalamine (Pentasa® and Salofalk®)
      may be as or more effective than twice daily dosing.

      To date, most RCTs have been conducted among adult patients and efficacy in children has been
      extrapolated from these data. However, childhood inflammatory bowel disease (IBD) may not be
      similar to adult onset disease. The prevalence of extensive colitis proximal to the splenic
      flexure is doubled in pediatric-onset UC compared to adults and extensive disease is
      consistently associated with more severe phenotype. On the other hand, studies in children
      with IBD often show better response to therapy than in adults. Therefore, American and
      European regulating agencies encourage pediatric studies be conducted for all approved drug
      products. It has been found that less than 50% of children with IBD are adherent with
      treatment, a figure associated with the understanding of the disease which is generally lower
      than in adults. Therefore, the advantage of once daily dosing of 5-ASA over twice-daily may
      be greater in children compares with adults.

      The investigators hypothesize that once daily dosing of mesalamine is superior in
      effectiveness to twice daily dosing to induce remission in pediatric mild-moderate UC. We
      base this hypothesis on data previously found in adults and due to the expected higher
      adherence rate.

      This study will compare two groups receiving an identical dose of the same non experimental
      medication, with the only difference being in the number of doses of the medication!
    

Intervention name(s): Mesalamine
Intervention type(s): Drug
Intervention description(s): Dosing: The current standard of care for pediatric UC is 75mg/kg/day of mesalamine (Pentasa) and should be in multiplications of 500mg (half sachets).
Patients will be randomized in blocks of six stratified by weight groups: 15- <30 kg, 30-40kg, >40kg.
For body wt. 15- <20kg Arm: Once daily, 1000 mg (morning) and Placebo (0.5 sachet) (evening). Arm: Twice daily, 500mg (morning) and 500mg (evening).
For body wt: 20- <30 kg Arm: Once daily, 1500mg (morning) and Placebo (0.5 sachet) (evening). Arm: Twice daily, 1000mg (morning) and 500mg (evening).
For Body wt. 30- <40 kg Arm: Once daily, 2000mg (morning) and Placebo (1 sachet) (evening). Arm: Twice daily, 1000mg (morning) and 1000mg (evening).
For body wt. ≥40 kg Arm: Once daily, 3000mg (morning) and Placebo (1.5 sachet) (evening). Arm: Twice daily, 1500mg (morning) and 1500mg (evening).
Intervention MeSH terms: Mesalamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: Pediatric; Ulcerative colitis; 5-ASA; Mesalamine; Dosing