Dose Escalation Clinical Trial of High-dose Oral Montelukast to Inform Future RCT in Children With Acute Asthma Exacerbations
Vanderbilt University Medical Center
Summary
This research will establish a mg/kg dose for a future RCT to determine the efficacy of high-dose oral montelukast for 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).
Description
Study design parameters Design: 2-arm, phase 3 double-blind RCT Intervention: Oral montelukast sprinkles or identical placebo Dose escalation: Doses between 2 mg/kg and 3 mg/kg based on pharmacokinetic modeling after each group of 5 participants. Montelukast is a potent LT-receptor antagonist and is FDA approved at a daily oral dose of 4-5 mg for chronic asthma and allergic rhinitis in children. It is also a potent bronchodilator. In randomized controlled trials (RCT) of adults with moderate and severe exacerbations and inadequate response to inhaled albuterol, intravenous (IV) montelukast ca…
Eligibility
- Age range
- 4–12 years
- Sex
- All
- Healthy volunteers
- No
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…
Interventions
- DrugMontelukast Oral Granules
Oral montelukast granules, USP powder, or crushed tablets at weight-based doses between 2 mg/kg and 3 mg/kg to a maximum of 180 mg.
- DrugAlbuterol
Inhaled albuterol by metered-dose inhaler (MDI) or nebulizer
- DrugCorticosteroid
Oral or parenteral corticosteroid (e.g., dexamethasone, methylprednisolone)
Location
- Monroe Carell Jr. Children's Hospital at VanderbiltNashville, Tennessee