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

NCT ID: NCT07101640

Last Updated: 2025-12-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-01
• Study Completion Date: 2028-05-31

Brief 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.

Detailed 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.

Conditions

Bronchopulmonary Dysplasia (BPD); Premature Births; Critical Illness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Montelukast Sodium

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.

Group Type: EXPERIMENTAL

montelukast 4 mg granule

Intervention Type: DRUG

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 .

Placebo

Plain breast milk or formula

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Plain breast milk or formula

Interventions

montelukast 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 .

Intervention Type: DRUG

Placebo

Plain breast milk or formula

Intervention Type: DRUG

Other Intervention Names

montelukast sodium

Eligibility 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

• Maximum Eligible Age: 28 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

R01HD113201

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00114044

Identifier Type: -

Identifier Source: org_study_id