The purpose of the study is to learn how safe montelukast may be in premature infants at significant risk for Bronchopulmonary Dysplasia (BPD) and to determine how much and how quickly montelukast moves from the stomach into the bloodstream, and how quickly it is removed from the bloodstream.
Data supporting the prospect of montelukast benefit involved 6 previous studies involving 206 preterm infants. The dosing ranged from 0.5 to 2.5 mg/kg/day, which aligns with the proposed initial dose of 0.75 mg/kg/day. Though each previous study had a small population, collectively they reveal montelukast as a promising drug in populations of preterm infants developing BPD and for individual preterm infants who are "developing BPD." Thus, researchers expect clinical benefit for preterm infants in this study.
Despite the benefit-to-risk ratio presented by these previous studies, the optimal dose remains to be determined; thus, this study design and PK analysis will start with the lowest dose that is likely to provide direct benefit to participants.
Documented informed consent from parent or guardian, prior to study activities
Receiving mechanical ventilation [high frequency or conventional] and requiring supplemental oxygen (FiO2 ≥ 30%) at time of randomization
<28 weeks' gestational age and <1000 g bodyweight at birth
7 to 28 (inclusive) days postnatal age at the time of first study drug dose
Previous enrollment and dosing in the current PRISM study (NICHD-2023-MON01)
Previous exposure to montelukast within 7 days prior to randomization
Known allergy to montelukast
PI deems infant - prior to enrollment - is not expected to survive
Parallel
montelukast 4 mg granule
DrugMontelukast sodium (4 mg oral granules) dissolved into 5mL of breast milk/formula yielding a solution concentration of 0.8mg/mL. Dosed once daily by weight, montelukast (0.75 mg/kg/day) or placebo .
Placebo
DrugPlain breast milk or formula
Apparent clearance (CL/F) of montelukast
The elimination of montelukast divided by the concentration of montelukast.
Volume of distribution
The total amount of montelukast in the body to the concentration in the bloodstream.
Half-life
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").
Area Under Curve (AUC)
The concentration of montelukast in blood plasma as a function of time.
Maximum Concentration (Cmax)
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.
Delirium Assessment
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 Bronchopulmonary Dysplasia (BPD)
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). 1. No BPD - receiving no respiratory support. 2. Mild (grade 1) BPD - receiving ≤2 L/min nasal cannula. 3. Moderate (grade 2) BPD - receiving \>2 L/min or non-invasive positive airway pressure. 4. Severe (grade 3) BPD - receiving invasive mechanical ventilation.
Time on supplemental oxygen
Duration in days that participant requires supplemental oxygen from the time of randomization.
Time on positive pressure ventilation
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).
Click on the lead sponsor to view all of their trials.
Duke University
Lead sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborator
University of North Carolina, Chapel Hill
Collaborator
University Medical Center of Southern Nevada
Collaborator
East Carolina University
Collaborator
University of Massachusetts, Worcester
Collaborator
Arkansas Children's Hospital Research Institute
Collaborator
