Use of Montelukast to Treat Children With Mild to Moderate Acute Asthma
Use of Montelukast to Treat Children With Mild to Moderate Acute Asthma
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.
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.
Inclusion Criteria:

 -  age 2-17 years

 -  Clinical diagnosis of mild to moderate asthma as a second wheezing episode associated
 with signs of respiratory distress suggesting lower airway obstruction such as
 tachypnea and/or use of accessory muscles of respiration.

 -  baseline Pulmonary Index Clinical Score (Appendix B) ≤ 11 out of 15 possible points as
 well as PRAM ≤ 8 out of 12 points.

 -  Presenting to the Sick Kids Emergency Department

 -  Children capable of FEV1 measurement will have FEV1 more than 60% of the predicted
 value

 -  male or female

 -  Willing and able to provide informed consent (or informed consent by parents)

 Exclusion Criteria:

 -  No previous history of wheezing or bronchodilator therapy. This population may
 eventually have diagnoses other than asthma or viral induced wheezing

 -  Patients who received more than a single dose of oral corticosteroids within 72 hours
 prior to arrival

 -  Patients receiving more than 500 mcg per day of fluticasone for more than 1 month or
 more than 250 mcg of fluticasone for more than 7 days prior to arrival

 -  Patients who have had more than 2 previous visits to the asthma clinic at SickKids

 -  Patients who received Montelukast within one week of arrival

 -  Critically ill patients requiring airway stabilization

 -  Patients with severe asthma, defined as PI 12 to 15 or PRAM 9 to 12.

 -  Co-existent co-morbidities such as chronic pulmonary disease and cardiac disease
 requiring pharmacotherapy, neurologic disease and immune disorders.

 -  Previous admission to ICU for asthma.

 -  More than 3 hospitalizations for asthma during the past 12 months.

 -  Contact with varicella within the previous 21 days.

 -  Insufficient command of the English language