Treating the Resistant Patent Ductus Arteriosus (PDA)

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 Overview

• Status: Unknown
• Conditions: Patent Ductus Arteriosus
• Intervention / Treatment: Drug: Indomethacin; Drug: Pentoxifylline

• Study Type: Interventional
• Enrollment (Anticipated): 68
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cathy Hammerman, MD; Phone Number: 9722 6666238; Email: cathy@cc.huji.ac.il

Study Locations

• Israel
  • Jerusalem, Israel, 91031
    • Neonatal Intensive Care Unit - Shaare Zedek Medical Center
    • Principal Investigator: Cathy Hammerman, MD
    • Sub-Investigator: Irina Schorrs, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Shaare Zedek Medical Center

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Anticipated): March 1, 2010

Study Registration Dates

• First Submitted: January 13, 2008
• First Submitted That Met QC Criteria: February 14, 2008
• First Posted (Estimate): February 15, 2008

Study Record Updates

• Last Update Posted (Estimate): February 15, 2008
• Last Update Submitted That Met QC Criteria: February 14, 2008
• Last Verified: January 1, 2008

More Information

Terms related to this study

• Keywords: PDA; pentoxifylline; indomethacin; Patent Ductus Arteriosus [PDA] resistant to therapy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Ductus Arteriosus, Patent; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Protective Agents; Reproductive Control Agents; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Gout Suppressants; Tocolytic Agents; Radiation-Protective Agents; Indomethacin; Pentoxifylline
• Other Study ID Numbers: CHPDA2