Treating the Resistant Patent Ductus Arteriosus (PDA)

Study Overview
=================
Brief Summary
-----------------
Persistent postnatal ductal patency may have significant adverse hemodynamic effects, frequently necessitating therapeutic intervention in order to facilitate ductal closure. Medical therapy for patency of the ductus arteriosus is successful mediating ductal closure in approximately 70% of treated infants. In a recent study in our population, 17% of the babies showed no ductal response to the first course of treatment and 9.4% of our study infants eventually underwent surgical ligation of the ductus after failure of medical therapeutic closure.We propose to evaluate and compare two alternate therapeutic approaches to ductal closure in babies who do not respond to initial therapy.

Official Title
-----------------
New Therapeutic Approaches to the Resistant Patent Ductus Arteriosus (PDA) in Low Birth Weight Neonates

Conditions
-----------------
Patent Ductus Arteriosus

Intervention / Treatment
-----------------
* Drug: Indomethacin
* Drug: Pentoxifylline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inborn premature neonates admitted to the neonatal intensive care unit of the Shaare Zedek Medical Center and diagnosed as having a hemodynamically significant patent ductus arteriosus (sPDA) will be considered as potential candidates for study if/when they do not respond to initial therapy Exclusion Criteria: Any baby not considered viable Any baby with 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 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
-----------------
Minimum Age: 2 Days
Maximum Age: 4 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stepwise Indo<br>Stepwise escalating doses of indomethacin, until ductal closure or maximum of 1 mg/kg/dose. | Drug: Indomethacin<br>* IV indomethacin starting at a dose of 0.4 mg/kg given over 30 minutes, increased daily by increments of 0.2 mg/kg/dose and given at intervals of 12 hours until a maximum dose of 1 mg/kg is reached, or until a total indomethacin dose of 6 mg/kg has been given. Daily echocardiography will be performed to monitor the progress of ductal closure. Once echocardiographic evidence of a closed ductus is achieved, two additional doses indomethacin will be given 24 hours and 48 hours later, using the same dose used in the last indomethacin infusion.<br>|
| Experimental: PTX<br>Combined administration of indomethacin and pentoxifylline, an inhibitor of TNF alpha | Drug: Pentoxifylline<br>* IV indomethacin will be re-started at a dose of 0.2 mg/kg to run over 30 minutes at 12 hour intervals to be given concurrently with pentoxifylline (5 mg/kg/hour to run over 6 hour once a day for a maximum of 6 days. Daily echocardiography will be performed to monitor the progress of ductal closure. Once echocardiographic evidence of a closed ductus is achieved, two additional doses indomethacin will be given 24 hours and 48 hours later and another day of pentoxifylline infusion, provided that the 6 day maximum has not yet been<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Our primary objective in this study is to improve ductal closure rates in those infants who do not respond to a first course of therapy. |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Our secondary objective is to compare the therapeutic efficacy of two very different secondary treatment protocols. |  | 2 years | 
| To monitor and compare potential side effects of the two treatment approaches |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PDA, indomethacin, pentoxifylline, Patent Ductus Arteriosus [PDA] resistant to therapy