Pharmacokinetics, Safety and Preliminary Efficacy Study of Montelukast in Critically Ill Infants With Developing Bronchopulmonary Dysplasia
Duke University
Summary
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.
Description
Multi-center, Prospective, Randomized, Double-masked, Placebo-Controlled Trial Participants (n=28) will be enrolled into a randomized, double-blinded, placebo-controlled trial of once daily montelukast (0.75 mg/kg/day) or placebo (1:1 allotment) for 7 days in critically ill premature infants with developing BPD. The overall aim is to characterize the pharmacokinetics (PK), short- and long-term adverse events (safety), and respiratory support changes (preliminary efficacy) with montelukast following once daily dosing for 7 days. Primary: Characterize the PK of montelukast in critically ill pr…
Eligibility
- Age range
- Up to 0 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria 1. Documented informed consent from parent or guardian, prior to study activities 2. Receiving mechanical ventilation \[high frequency or conventional\] and requiring supplemental oxygen (FiO2 ≥ 30%) at time of randomization 3. \<28 weeks' gestational age and \<1000 g bodyweight at birth 4. 7 to 28 (inclusive) days postnatal age at the time of first study drug dose 5. Able to tolerate 5 mL of enteral volume Exclusion Criteria 1. Previous enrollment and dosing in the current PRISM study (NICHD-2023-MON01) 2. Previous exposure to montelukast within 7 days prior to randomiza…
Interventions
- Drugmontelukast 4 mg granule
Montelukast 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 .
- DrugPlacebo
Plain breast milk or formula
Locations (4)
- Arkansas Children's HospitalLittle Rock, Arkansas
- University Medical Center of Southern NevadaLas Vegas, Nevada
- University of North Carolina (UNC)Chapel Hill, North Carolina
- East Carolina UniversityGreenville, North Carolina