Safety/Efficacy Study of Optimizing Ibuprofen Dosing to Achieve Higher PDA Closure Rates

Study Overview
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Brief Summary
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The purpose of this study is to determine if increasing the ibuprofen dose will increase the likelihood of closing the patent ductus arteriosus in premature babies.

Detailed Description
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Failure to close the PDA in premature neonates in a timely fashion can lead to pulmonary over-circulation and systemic under-circulation. The PDA often fails to close using currently approved Ibuprofen dosing regimens, and surgical closure becomes necessary. Ibuprofen clearance in premature neonates is significantly correlated with postnatal age, increasing rapidly over time. Hirt et al. published and optimized dosing scheme for preterm neonates based on pharmacokinetic and pharmacodynamic data. We aim to use this dosing regimen in the clinical setting to determine if increased rates of pharmacologic PDA closure can be achieved.

Official Title
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Safety and Efficacy of an Optimized Ibuprofen Dosing Regimen Versus Standard Dosing for Pharmacologic Closure of Patent Ductus Arteriosus

Conditions
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Patent Ductus Arteriosus

Intervention / Treatment
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* Drug: optimized ibuprofen
* Drug: Standard Ibuprofen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All neonates (0-29 days old) less than or equal to 33 post-menstrual age at time of PDA diagnosis requiring nasal CPAP or mechanical ventilation Echo confirmed PDA with a transductal diameter of 1.5 mm or greater and demonstrating a left-to-right shunt Signed informed consent Exclusion Criteria: Presence of: ductal-dependent congenital heart disease, pulmonary hypertension, Active bleeding (including Grade 3 or 4 IVH) Platelet count < 100,000 Coagulopathy Suspected NEC Suspected perforation Creatinine > 1.5 Hyperbilirubinemia requiring exchange transfusion Hypotension requiring pressor support Life-threatening congenital malformation

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 29 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Optimized Ibuprofen<br> | Drug: optimized ibuprofen<br>* day of life 0-3 - 10, 5, 5 mg/kg/dose at 24 hour intervals day of life 4-6 - 14, 7, 7 mg/kg/dose at 24 hour intervals day of life 7-29 - 20, 10, 10 mg/kg/dose at 24 hour intervals<br>* Other names: neoprofen;|
| Active Comparator: Standard Ibuprofen<br> | Drug: Standard Ibuprofen<br>* day of life 0-29 - 10,5, 5 mg/kg/dose at 24 hour intervals<br>* Other names: neoprofen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PDA Closure |  | 1-42 days of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| renal function |  | 1-30 days of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PDA, Ibuprofen, Preterm, Neonate