PK, Safety and Preliminary Efficacy Study of Montelukast in Critically Ill Infants With Developing Bronchopulmonary Dysplasia

The elimination of montelukast divided by the concentration of montelukast.

The total amount of montelukast in the body to the concentration in the bloodstream.

The time that it takes for the concentration of montelukast in blood plasma to reach one-half of its steady-state value (the "plasma half-life").

The concentration of montelukast in blood plasma as a function of time.

The maximum (or peak) serum concentration that montelukast achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose.

All infants who die at or before 30 days post treatment or 36 weeks PMA, whichever is longer, will be enumerated by treatment group. Researchers will also summarize by treatment group the percent and cumulative incidence of deaths through 24 months of follow-up.

Total SAEs by participants. Researchers will determine the incidence (rate per person-time) and prevalence (percent of each treatment group experiencing an SAE) at or before 30 days post treatment or 36 weeks PMA, whichever is longer.

Researchers will collect safety events of special interest: neuropsychiatric events, including irritability, sedation, apnea, convulsion/seizure, sleep disturbance, tremor and neuropsychiatric event (other). 'Other' will be any event not fitting the previous categories but deemed to be neuropsychiatric in nature by the site principal investigator (PI). For total NPAEs, researchers will determine the incidence (rate per person-time) and prevalence (percent of each treatment arm experiencing an NPAE) for each treatment group. For all safety events researchers will calculate the incidence and prevalence for both the treatment period and for the period to 30 days post treatment or 36-weeks PMA, whichever is longer. Site investigators will determine seriousness and severity for all AEs.

Researchers will determine the prevalence (percent of each treatment group experiencing an infectious adverse event) at or before 30 days post treatment or 36 weeks PMA, whichever is longer. Specific infections will include (but not limited to): upper respiratory infections, pharyngitis, sinusitis, and otitis.

The Bayley Scales of Infant and Toddler Development, Fourth Edition, (often referred to as the Bayley-4) will be completed by a site-based specialist at 24 months of age (range 22 to 26 months). The Bayley-4 is a standardized assessment tool designed to evaluate the developmental functioning of infants and toddlers. Composite scores for each domain are standardized, with a mean of 100 and a standard deviation of 15. Composite scores are also converted into percentile ranks, which indicate the child's performance relative to a normative sample. For instance, a percentile rank of 50 means the child is performing at the average level for their age group.

The Ages and Stages Questionnaires (ASQ) is a developmental screening tool designed to assess the developmental progress of children from one month to 5 ½ years of age. For each of the 5 domains assessed by the ASQ, the minimum score is 0 and maximum score is 60. Higher scores mean better outcome.

The Child Behavior Checklist (CBCL) is a widely used tool for assessing behavioral and emotional problems in children as young as infancy and toddlerhood.

Oxygen saturation index (OSI) is used to assess the severity of respiratory failure. A higher OSI value indicates worse respiratory compromise. The main OSI endpoint will be the change from randomization baseline to day 7 of treatment.

The Cornell Assessment of Pediatric Delirium (CAPD) will be completed in infants at 36 weeks PMA who remain hospitalized. This tool involves scoring based on observations over several hours, rather than a single point in time. A score of 9 or higher typically indicates the presence of delirium.

Clinical BPD will be determined and graded based on clinical severity, which will be based on respiratory support (supplemental oxygen or positive airway pressure) needed at 36 weeks' PMA. This outcome will be measured on a 4-level ordinal scale (as a-d below) and on a dichotomous scale (moderate-to-severe BPD vs. no BPD/mild BPD).

• No BPD - receiving no respiratory support.
• Mild (grade 1) BPD - receiving ≤2 L/min nasal cannula.
• Moderate (grade 2) BPD - receiving >2 L/min or non-invasive positive airway pressure.
• Severe (grade 3) BPD - receiving invasive mechanical ventilation.

Duration in days that participant requires supplemental oxygen from the time of randomization.

Duration in days that participant requires positive airway pressure (any type of mechanical ventilation or continuous positive airway pressure (CPAP) or high-flow nasal cannula >1 L/min flow) from the time of randomization. Researchers will also collect time specifically requiring mechanical ventilation (conventional ventilation or hi-frequency ventilation).

All infants who died at or before 36 weeks PMA will be included

All infants who die during the course of the study.