Treating Exacerbations of Asthma With Oral Montelukast in Children

Description

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).

Conditions

Status Asthmaticus

Study Overview

Study Details

Study overview

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).

Dose Escalation Clinical Trial of High-dose Oral Montelukast to Inform Future RCT in Children With Acute Asthma Exacerbations

Treating Exacerbations of Asthma With Oral Montelukast in Children

Condition
Status Asthmaticus
Intervention / Treatment

-

Contacts and Locations

Nashville

Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee, United States, 37232-9001

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility 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.
  • * 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.

Ages Eligible for Study

4 Years to 12 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

Vanderbilt University Medical Center,

Donald H Arnold, MD, MPH, PRINCIPAL_INVESTIGATOR, Vanderbilt University School of Medicine

Study Record Dates

2025-10-31