Treating Exacerbations of Asthma With Oral Montelukast in Children

• Status: Not yet recruiting
• Trial end date: 2025-07-21
• Target enrollment: 0
• Participant gender: All

Summary

Pediatric acute asthma exacerbations frequently do not respond to standard treatment of systemic corticosteroid and inhaled albuterol due to leukotriene-mediated airway inflammation that does not respond to these medications. Montelukast is a leukotriene inhibitor, and intravenous (IV) montelukast caused rapid improvements in adults with exacerbations, though the IV form is not available. The investigators' pilot pharmacokinetic (PK) study indicates that oral montelukast at a dose higher than currently used for preventing allergies achieves plasma levels similar to the IV preparation. This study will examine escalating mg/kg doses of montelukast to determine an optimal dose and will provide preliminary efficacy data to inform a future clinical trial sufficiently powered to determine efficacy in children with moderate and severe acute asthma exacerbations.

Aim: Perform an adaptive, double-masked randomized controlled trial (RCT) of high-dose oral montelukast, with escalating mg/kg dose levels determined by PK-guided dose modeling, added to standard treatment versus standard treatment alone, in children with exacerbations that are moderate or severe after initial treatment with inhaled albuterol.

Hypothesis 1: High-dose oral montelukast achieves peak plasma concentration (Cmax) >1,700 ng/ml in >86% of at least one of three sequential participant groups with escalating weight-based (milligram/kilogram or mg/kg) doses between groups.

Hypothesis 2: Participants randomized to high-dose oral montelukast have a 2 point or greater improvement of the validated Acute Asthma Intensity Research Score (AAIRS) at 4 hours post-treatment in comparison with control group participants.

Hypothesis 3: Among montelukast recipients, Cmax correlates with change of the AAIRS at 4 hours, after adjustment for pre-treatment exacerbation severity and systemic leukotriene stress measured using urinary leukotriene E4 (LTE4).

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

Details

• Lead Sponsor: Vanderbilt University Medical Center
• Treatments: Albuterol; Montelukast

Criteria

Inclusion Criteria:

• Child aged 4 - 12 years with doctor-diagnosed asthma

• Presents to the Vanderbilt Children's Hospital with an acute asthma exacerbation that is moderate or severe (AAIRS >7) after initial treatment with inhaled albuterol

• The parent agrees to phone and/or mail follow-up at 2-3 weeks for completion of SCARED and side-effect questionnaires.

Exclusion Criteria:

• Gestational age < 34 weeks

• acute or chronic liver disease

• allergy to montelukast

• female with any evidence of Tanner stage 2 or greater breast development

• gastroesophageal reflux requiring acid-blocking medication

• history of anxiety disorder, depression and/or other neuropsychiatric disorder except ADHD

• positive on question 1 or 2 of the Columbia Suicide Severity Rating Scale (CSSR-S)

• score >25 on the 82-point Screen for Child Anxiety Related Disorders (SCARED) questionnaire

• Patients currently receiving daily montelukast (4 or 5 mg) will not be excluded from study participation.