Second Course of Therapy for Resistant Patent Ductus Arteriosus (PDA)

Study Overview
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Brief Summary
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Patency of the ductus arteriosus (PDA) is functionally essential for fetal circulation, however persistence of ductal patency postnatally may have significant adverse hemodynamic effects in the neonate. Medical therapy for PDA predominantly involves the administration of one of two non-steroidal anti-inflammatory drugs: indomethacin or ibuprofen. Both of these therapies have been shown to be successful in mediating ductal closure in approximately 70% of treated infants. However, the need for a second course of treatment for PDA closure remains quite common. The investigators hypothesize that, because of small differences between the two drugs, a greater percentage of infants who did not respond to a first course of therapy with indomethacin will respond to a second course with ibuprofen than to a repeat course of indomethacin. As such, the investigators aim to compare secondary therapy with a repeat course of indomethacin to secondary therapy with ibuprofen in infants whose ductus remained patent after a first course of therapy with indomethacin.

Official Title
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Ibuprofen vs. Indomethacin as Second Course of Therapy for Resistant PDA in Low Birth Weight Neonates

Conditions
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Patent Ductus Arteriosus

Intervention / Treatment
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* Drug: Indomethacin
* Drug: Ibuprofen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inborn premature neonates (birth weight [BW] <1500 grams) being treated in the neonatal intensive care unit of the Shaare Zedek Medical Center and diagnosed as still having a hemodynamically significant patent ductus arteriosus (hsPDA) after a first course of therapy with indomethacin, will be considered as potential candidates for study pending response to initial therapy and pending parental consent. Exclusion Criteria: Any baby not considered viable Any baby with intraventricular hemorrhage (IVH) grade 3-4 of recent onset (within 3 days). [If no head ultrasound has been performed within the last 3-4 days, one should be performed prior to onset of study.] Any baby with dysmorphic features or congenital abnormalities Any baby with structural heart disease other than PDA Any baby with documented infection, Any baby with thrombocytopenia (<50,000).

Ages Eligible for Study
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Minimum Age: 2 Days
Maximum Age: 2 Months

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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indomethacin for resistant PDA<br>Treatment with second course of indomethacin | Drug: Indomethacin<br>* Three doses of intravenous (IV) indomethacin at 0.2 mg/kg/dose given over 30 minutes, at intervals of 12 hours<br>* Other names: Indomed;|
| Experimental: Ibuprofen for resistant PDA<br>Ibuprofen as second course of therapy | Drug: Ibuprofen<br>* 10 mg/kg infused over 30 minutes, followed by two doses of 5mg/kg each at 24 hour intervals<br>* Other names: Arfen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in ductal closure rates in those infants who do not respond to a first course of therapy |  | 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| More infants who did not respond to a first course of therapy with indomethacin who respond to a second course with ibuprofen than to a repeat course of indomethacin |  | 2.5 years | 
| Secondary treatment with ibuprofen, as opposed to indomethacin, will not be associated with increased side effects |  | 2.5 years | 

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