Treating Exacerbations of Asthma With Oral Montelukast in Children

NCT05819541 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: R34HL168301
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Status Asthmaticus

Outcome Measures

Primary Outcomes (1)

• Montelukast plasma level

  Peak montelukast plasma level

  4 hours

Secondary Outcomes (2)

• Change of Acute Asthma Intensity Research Score

  4 hours

• Airway resistance by impulse oscillometry (IOS)

  4 hours

Study Arms (2)

High-dose oral montelukast plus standard treatment

EXPERIMENTAL

Escalating dose-levels of oral montelukast between 2 mg/kg and 3 mg/kg determined by pharmacokinetic-guided dose modeling, added to standard, guideline-based treatment (systemic corticosteroid, inhaled albuterol, and possible treatment adjuncts such as IV magnesium, determined by evidence-based asthma clinical practice guideline).

Drug: Montelukast Oral Granules; Drug: Albuterol; Drug: Corticosteroid

Identical placebo plus standard treatment

PLACEBO COMPARATOR

Guideline-based treatment (systemic corticosteroid, inhaled albuterol, and possible treatment adjuncts such as IV magnesium, determined by evidence-based asthma clinical practice guideline).

Drug: Albuterol; Drug: Corticosteroid

Interventions

Montelukast Oral Granules DRUG

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.

Also known as: Singulair

High-dose oral montelukast plus standard treatment

Albuterol DRUG

Inhaled albuterol by metered-dose inhaler (MDI) or nebulizer

Also known as: Inhaled albuterol

High-dose oral montelukast plus standard treatment; Identical placebo plus standard treatment

Corticosteroid DRUG

Oral or parenteral corticosteroid (e.g., dexamethasone, methylprednisolone)

Also known as: Systemic corticosteroid

High-dose oral montelukast plus standard treatment; Identical placebo plus standard treatment

Eligibility Criteria

• Age: 4 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232-9001, United States

RECRUITING

Related Publications (3)

• Arnold DH, Bowman N, Reiss TF, Hartert TV, Seger DL. Adverse events are rare after single-dose montelukast exposures in children. Clin Toxicol (Phila). 2018 Jan;56(1):25-29. doi: 10.1080/15563650.2017.1337123. Epub 2017 Jun 22.

  PMID: 28639856 RESULT

• Arnold DH, Bowman N, Reiss TF, Hartert TV, Akers WS, Seger DL. Adverse events associated with weight-based, high-dose montelukast exposures in children. Clin Toxicol (Phila). 2020 Feb;58(2):145-146. doi: 10.1080/15563650.2019.1609686. Epub 2019 May 6. No abstract available.

  PMID: 31056949 RESULT

• Arnold DH, Van Driest SL, Reiss TF, King JC, Akers WS. Pilot Study of Peak Plasma Concentration After High-Dose Oral Montelukast in Children With Acute Asthma Exacerbations. J Clin Pharmacol. 2021 Mar;61(3):360-367. doi: 10.1002/jcph.1738. Epub 2020 Sep 22.

  PMID: 32960980 RESULT

MeSH Terms

Conditions

Status Asthmaticus

Interventions

montelukast; Albuterol; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Donald H Arnold, MD, MPH

  Vanderbilt University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Donald H Arnold, MD, MPH

CONTACT

16155790516; don.arnold@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: We will use randomly-permuted 1:1 blocks of 10 to minimize seasonal bias of exacerbation precipitants that may have independent associations with treatment-response. The study biostatistician will use the randomizeR package in R statistical software to provide the randomization schedule. A Research Electronic Data Capture (REDCap) database will be built that will incorporate the randomization sequence. When the investigators place an electronic medical record order (eStar) order for drug, the randomization database will designate randomized treatment allocation to the pharmacy. Pharmacy will prepare appropriate drug. The REDCap database will email and text the study pharmacist performing plasma assays, pharmacy staff, and the investigators 24 hours after the 5th participant is randomized to MK within each dose group. This will alert the investigators to pause enrollment until MK assays are completed and the mg/kg MK dose is determined for the next dose group.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics and Emergency Medicine

Model Details: The aim is to perform an adaptive, double-masked, 2-arm RCT of high-dose oral montelukast, with 3 sequential, escalating dose-levels determined by PK-guided dose modeling, added to standard treatment versus standard treatment alone, in children with asthma exacerbations that are moderate or severe after initial treatment with inhaled albuterol.

Study Record Dates

• First Submitted: March 24, 2023
• First Posted: April 19, 2023
• Study Start: October 20, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)