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

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, in children aged 5 to 17 years with moderate and severe acute asthma exacerbations.

Intervention: High-dose oral montelukast added to standard treatment 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).

Conditions

• Asthma; Status
• Asthma in Children
• Asthma Acute
• Asthma Attack
• Acute Asthma Exacerbation

Interventions

DRUG

Montelukast Oral Granules

Montelukast granules, 30 mg, mixed with applesauce

Sponsors & Collaborators

• Vanderbilt University Medical Center

  lead OTHER

Principal Investigators

• Donald H Arnold, MD, MPH · Vanderbilt University School of Medicine, Department of Pediatrics

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

5 Years

Max Age

17 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-09-01

Primary Completion

2028-08-31

Completion

2029-09-05

FDA Drug

Yes

Countries

• United States

Study Locations