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

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: March 2010

Intervention(s) in this Clinical Trial

• Drug: Indomethacin
  • 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.
• Drug: Pentoxifylline
  • 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

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Stepwise Indo
  • Stepwise escalating doses of indomethacin, until ductal closure or maximum of 1 mg/kg/dose.
• Experimental: PTX
  • Combined administration of indomethacin and pentoxifylline, an inhibitor of TNF alpha

Primary Measures

• 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.
  • Time Frame: 2 years
    Safety Issue?: No

Secondary Measures

• Our secondary objective is to compare the therapeutic efficacy of two very different secondary treatment protocols.
  • Time Frame: 2 years
    Safety Issue?: No
• To monitor and compare potential side effects of the two treatment approaches
  • Time Frame: 2 years
    Safety Issue?: Yes

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).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 4 Weeks

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Shaare Zedek Medical Center

Overall Clinical Trial Officials and Contacts

Cathy Hammerman, MD Principal Investigator Shaare Zedek Medical Center  

Overall Contact: Cathy Hammerman, MD 9722 6666238 cathy@cc.huji.ac.il

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00616382

Study ID Number: CHPDA2

ClinicalTrials.gov Identifier: NCT00616382

Health Authority: Israel: Ministry of Health