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

R34HL168301

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).

2023-10-20

2025-06-30

2025-10-31

Recruiting

Early phase I

90

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 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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': '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.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'maskingDescription': '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.', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 90, 'type': 'ESTIMATED'}}

2024-05-14