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

Duke University

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Premature Births; Bronchopulmonary Dysplasia (BPD); Critical Illness

Treatments: Drug: Placebo; Drug: montelukast 4 mg granule

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07101640

Pro00114044

R01HD113201 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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 premature infants with developing bronchopulmonary dysplasia (BPD).

Secondary: Describe the acute safety profile of montelukast and 2-year developmental progress in critically ill premature infants with developing BPD.

Tertiary: Determine preliminary efficacy of montelukast in critically ill premature infants with developing BPD.

Inpatient participation: Will vary based on gestational age and age at randomization; Up to approximately 60 days (7 days of study drug plus 30 days of post-drug safety monitoring or to 36 weeks postmenstrual age, whichever is longer).

Outpatient participation: Medical and neurodevelopmental follow-up assessments at 6, 12, 18 and 24 months old.

Enrollment: 28 estimated patients

Sex: All

Ages: Under 28 weeks old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 randomization
3. Known allergy to montelukast
4. PI deems infant - prior to enrollment - is not expected to survive
5. Has a disease complication that would preclude safe participation of the participant
6. Increased respiratory support due to intercurrent illness (e.g., sepsis, necrotizing enterocolitis, etc.). Infants should be excluded from the study until after resolution of the acute event
7. Congenital lung and diaphragmatic malformations

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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28 participants in 2 patient groups, including a placebo group

Montelukast Sodium

Experimental group

Description:

Once daily montelukast dosed at 0.75 mg/kg/day, maximum dose 4mg. 4mg of montelukast mixed in 5mlL breast milk/formula for a concentration of 0.8mg/mL.

Treatment:

Drug: montelukast 4 mg granule

Placebo

Placebo Comparator group

Description:

Plain breast milk or formula

Treatment:

Drug: Placebo