Use of Montelukast to Treat Children With Mild to Moderate Acute Asthma

This study has been completed.
Sponsor:
Collaborator:
Merck Frosst Canada Ltd.
Information provided by (Responsible Party):
Suzanne Schuh, The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT00213252
First received: September 13, 2005
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Asthma, Bronchial
Drug: Montelukast plus prednisolone
Drug: Prednisolone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Can Montelukast Shorten Corticosteroid Therapy In Children With Mild To Moderate Acute Asthma?

Resource links provided by NLM:


Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:
  • Therapeutic failure rate [ Time Frame: From randomization at discharge from the Emergency Department to day 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of inhaled salbutamol treatments [ Time Frame: From randomization to 24, 48, 72, 96, 120, 144 hours and day 8 ] [ Designated as safety issue: No ]
  • Change in the daytime asthma symptom scale from randomization [ Time Frame: 48 hours and Day 8 ] [ Designated as safety issue: No ]
  • Change in the nighttime cough [ Time Frame: 8 days ] [ Designated as safety issue: No ]
  • Number of days without asthma [ Time Frame: 8 days ] [ Designated as safety issue: No ]
  • Change in the Pulmonary Index Score from baseline [ Time Frame: 48 hours and Day 8 ] [ Designated as safety issue: No ]
  • Change in the Pediatric Respiratory Assessment Measure(PRAM)from baseline [ Time Frame: 48 hours and Day 8 ] [ Designated as safety issue: No ]
  • Association between the main treatment effect and patients' age, disease severity at randomization (Pulmonary Index and PRAM) and personal/family history of atopy. [ Time Frame: 48 hours and Day 8 ] [ Designated as safety issue: No ]

Enrollment: 130
Study Start Date: September 2005
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Montelukast plus prednisolone
Single dose of oral prednisolone with a subsequent daily five-day course of oral Montelukast
Active Comparator: 2 Drug: Prednisolone
Six daily doses of oral prednisolone

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.

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00213252

Locations
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
The Hospital for Sick Children
Merck Frosst Canada Ltd.
Investigators
Principal Investigator: Suzanne Schuh, MD The Hospital for Sick Children, Toronto, Canada
  More Information

Publications:
Responsible Party: Suzanne Schuh, Staff Physician, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT00213252     History of Changes
Other Study ID Numbers: 1000007674
Study First Received: September 13, 2005
Last Updated: May 12, 2014
Health Authority: Canada: Health Canada

Keywords provided by The Hospital for Sick Children:
asthma, randomized trial, pediatrics

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Methylprednisolone acetate
Prednisolone acetate
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Montelukast
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 18, 2014