Use of Montelukast to Treat Children With Mild to Moderate Acute Asthma
Condition: Asthma, Bronchial
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary objective of this study is to evaluate if children with acute asthma given a
      single dose of oral prednisolone with a subsequent daily five-day course of oral Montelukast
      will achieve a therapeutic failure rate at day 8 not significantly higher than those given
      six daily doses of oral prednisolone. Secondary objectives include comparison of the two
      groups with respect to the changes in symptoms, beta2 agonists, clinical asthma score and
      days without asthma by day 8.
    

Detailed description: 
      We plan a randomized double blind double-dummy trial of 190 previously healthy children 2-17
      years of age presenting to the Emergency Department (ED) at the Hospital for Sick Children in
      Toronto with mild to moderate acute asthma, with the Pulmonary Index score ≤ 11 points and
      PRAM ≤ 8 points. Asthma will be defined as at least the second episode of wheezing, with
      signs of lower airway obstruction. All participating children will receive a single dose of
      oral prednisolone 2mg/kg (max 60 mg) on arrival and standardized inhaled salbutamol in the ED
      and for five days thereafter. At discharge from ED children will be randomized to two
      interventional groups. Those in the Montelukast group will get oral Montelukast 4 mg (2-5
      year olds), 5 mg (6-14 year olds), and 10 mg (15-17 year olds) as well as daily
      prednis(ol)one placebo 24 hours after the ED dose of prednisolone and at 48, 72, 96 and 120
      hours, while those in the prednisolone group will receive Montelukast placebo and daily oral
      prednisolone 1mg/kg (max 60 mg) for five further doses at these times.

      The primary outcome will be therapeutic failure in the two groups from randomization to day
      8. This failure will be defined as unscheduled medical visits for asthma symptoms or
      hospitalization or treatment with oral corticosteroids outside the experimental protocol.
      Secondary outcome measures include comparison of the number of salbutamol treatments, changes
      in the previously validated daytime symptoms scale, nighttime cough/awakening scale, number
      of asthma-free days within the 8 day observational period in the two groups, changes in the
      PI and PRAM scores to 48 hours and day 8 as well as the association between the main
      treatment effect and age, pulmonary index at randomization and history of atopy.

      This study will take two 9 months periods. Primary analysis will include a one-sided 95% CI
      for the difference in failure rate in the prednisolone group minus the Montelukast group.
      Secondary analyses will include repeated measures ANOVA for differences in changes of
      continuous variables and the Fisher's Exact test for comparison of proportions. An
      exploratory sub-group logistic regression analysis will be done for examining interaction
      between the main treatment effect and possible covariates.

      In the event that the patients given a single dose of prednisolone followed by Montelukast
      have comparable therapeutic failure rate to those given standard extended prednisolone
      therapy, administration of Montelukast may help us abbreviate the length of corticosteroid
      therapy in children with acute asthma.
    

Intervention name(s): Montelukast plus prednisolone; Prednisolone
Intervention type(s): Drug; Drug
Intervention description(s): Single dose of oral prednisolone with a subsequent daily five-day course of oral Montelukast; Six daily doses of oral prednisolone
Intervention MeSH terms: Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Montelukast; Prednisolone hemisuccinate; Prednisolone phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: asthma, randomized trial, pediatrics