Pharmacokinetics, Safety and Preliminary Efficacy Study of Montelukast in Critically Ill Infants With Developing Bronchopulmonary Dysplasia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 28
- 试验地点
- 5
- 主要终点
- Apparent clearance (CL/F) of montelukast
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 7 Days 至 28 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Able to tolerate 5 mL of enteral volume
排除标准
- •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
- •Has a disease complication that would preclude safe participation of the participant
- •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
- •Congenital lung and diaphragmatic malformations
研究组 & 干预措施
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.
干预措施: montelukast 4 mg granule (Drug)
Placebo
Plain breast milk or formula
干预措施: Placebo (Drug)
结局指标
主要结局
Apparent clearance (CL/F) of montelukast
时间窗: From enrollment to 14 days post first dose.
The elimination of montelukast divided by the concentration of montelukast.
次要结局
- Volume of distribution(From first dose of study drug though 7 days post last dose.)
- Half-life(From first dose of study drug though 7 days post last dose.)
- Area Under Curve (AUC)(From first dose of study drug though 7 days post last dose.)
- Maximum Concentration (Cmax)(From first dose of study drug though 7 days post last dose.)
- Death- Safety(From 30 days post treatment or 36 weeks PMA, whichever is longer; through 24 months of follow-up.)
- Serious Adverse Events(At or before 30 days post treatment or 36 weeks PMA, whichever is longer.)
- Total Neuropsychiatric Adverse Events (NPAE)(From first dose to 30 days post treatment or 36-weeks PMA, whichever is longer.)
- Neonatal Infections(From first dose till at or before 30 days post treatment or 36 weeks PMA, whichever is longer.)
- Neurodevelopmental outcomes (Bayley-4)(From first dose through 24 months of age.)
- Neurodevelopmental outcomes (Ages and Stages Questionnaires (ASQ))(6 months, 12 months, 18 months, and 24 months)
- Neurodevelopmental outcomes (Child Behavior Checklist (CBCL)(18 months, 24 months)
- Oxygen saturation index (OSI)(From randomization baseline to day 7 of treatment.)