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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Stepwise Indo | Experimental | Stepwise escalating doses of indomethacin, until ductal closure or maximum of 1 mg/kg/dose. |
|
| PTX | Experimental | Combined administration of indomethacin and pentoxifylline, an inhibitor of TNF alpha |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Indomethacin | Drug | 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. |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Cathy Hammerman, MD | Contact | 9722 6666238 | cathy@cc.huji.ac.il |
| Name | Affiliation | Role |
|---|---|---|
| Cathy Hammerman, MD | Shaare Zedek Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Neonatal Intensive Care Unit - Shaare Zedek Medical Center | Jerusalem | 91031 | Israel |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16322159 | Result | Sperandio M, Beedgen B, Feneberg R, Huppertz C, Brussau J, Poschl J, Linderkamp O. Effectiveness and side effects of an escalating, stepwise approach to indomethacin treatment for symptomatic patent ductus arteriosus in premature infants below 33 weeks of gestation. Pediatrics. 2005 Dec;116(6):1361-6. doi: 10.1542/peds.2005-0293. | |
| 8618179 |
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| ID | Term |
|---|---|
| D004374 | Ductus Arteriosus, Patent |
| ID | Term |
|---|---|
| D006330 | Heart Defects, Congenital |
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
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| ID | Term |
|---|---|
| D007213 | Indomethacin |
| D010431 | Pentoxifylline |
| ID | Term |
|---|---|
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Pentoxifylline | Drug | 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 |
|
| Gonzalez A, Sosenko IR, Chandar J, Hummler H, Claure N, Bancalari E. Influence of infection on patent ductus arteriosus and chronic lung disease in premature infants weighing 1000 grams or less. J Pediatr. 1996 Apr;128(4):470-8. doi: 10.1016/s0022-3476(96)70356-6. |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D013805 | Theobromine |
| D014970 | Xanthines |
| D011688 | Purinones |
| D011687 | Purines |