Treating Exacerbations of Asthma With Oral Montelukast in Children
Status:
Not yet recruiting
Trial end date:
2025-07-21
Target enrollment:
Participant gender:
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).