Pragmatic RCT of High-dose Oral Montelukast for Moderate and Severe Pediatric Acute Asthma Exacerbations

• Status: Not yet recruiting
• Trial end date: 2023-09-05
• Target enrollment: 0
• Participant gender: All

Summary

Objective: To determine the extent to which high-dose (30mg) oral montelukast, added to standard treatment in children with moderate and severe acute exacerbations improves outcomes.

Central Hypothesis: High-dose oral montelukast, added to standard treatment in children aged 5 to 17 years with moderate and severe acute asthma exacerbations, rapidly improves lung function, clinical severity, hospitalization rate and 72-hour symptom burden.

Secondary Hypotheses:

1. There are greater effects of high-dose oral montelukast on lung function and on the secondary outcomes in the presence of respiratory viral detection or leukotriene-mediated inflammation; and

2. There is an interaction between viral detection and urinary leukotriene 4 level with treatment-response.

Design: A two-arm, parallel randomized controlled trial of high-dose oral montelukast versus identical placebo, as add-on to standard treatment of systemic corticosteroid (SCS) and inhaled short-acting Beta-2-agonist (SABA), in children aged 5 to 17 years with moderate and severe acute asthma exacerbations.

Intervention: High-dose oral montelukast added to standard treatment as one treatment-allocation arm, in comparison with standard treatment as the 2nd treatment-allocation arm.

Primary and Important Secondary Endpoints: For the Primary Aim, the primary outcome measure to be compared between arms will be change of %-predicted airway resistance by impulse oscillometry (IOS) at 5Hz (%R5) at 2 hours after treatment initiation. Secondary outcomes will include improvement of %-predicted FEV1 (%FEV1), clinical severity measured using the validated Acute Asthma Intensity Research Score (AAIRS), hospitalization rate, and 72 hour symptom burden using the Pediatric Asthma Caregiver Diary (PACD). For the Secondary Aim, the investigators will determine (1) The effects of high-dose oral montelukast on lung function and on our secondary outcomes in the presence of nasal viruses and of greater leukotriene-mediated inflammation; and (2) The degree of interaction between viral detection and urinary leukotriene E4 (LTE4) level with treatment-response.

Laboratory evaluations: The primary outcome (change of %R5) and select secondary outcomes (%FEV1, AAIRS, LTE4) will be measured before and again at 2 hours after treatment initiation. The other secondary outcomes will be measured at the time of hospitalization decision-making by the clinical team (hospitalization rate) or at 72-hours after treatment initiation (PACD).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University Medical Center
• Collaborator: National Institutes of Health (NIH)
• Treatments: Montelukast

Criteria

Inclusion criteria:

• Age 5 to 17 years, inclusive

• Parental report of asthma diagnosis by a health care provider

• At least one previous wheezing episode treated with albuterol

• Moderate or severe acute asthma exacerbation measured using the validated AAIRS bedside asthma severity score

Exclusion criteria:

• Prior study enrollment

• Chronic lung disease other than asthma

• History of prematurity less than 34 weeks gestational age

• Acute or chronic liver disease

• Presence of tracheostomy

• Use of noninvasive ventilation at home

• Need for immediate airway intervention (e.g., endotracheal intubation or noninvasive ventilation)

• Allergy to montelukast

• Pregnancy

• Tuberculosis

• Gastroesophageal reflux requiring acid-blocking medication; and

• Prior use of an LTRA (e.g., montelukast)