Treating Exacerbations of Asthma With Oral Montelukast in Children
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 pre-treatment plasma leukotriene E4 (LTE4).
Timeline
- Start
- 2023-10-20
- Primary completion
- 2026-03-26
- Completion
- 2026-03-26
Publications
- Results 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.
- Results 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.
- Results 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.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Montelukast | Other / unclassified | 2 mg/kg | Oral |
| Subject | Montelukast | Other / unclassified | 3 mg/kg | Oral |
| Background | Dexamethasone | Small molecule | — | Oral |
| Background | Methylprednisolone | Other / unclassified | — | Oral |
| Background | Salbutamol | Unknown | — | Inhaled |