Treating the Resistant Patent Ductus Arteriosus (PDA) - Full Text View

Sponsor:	Shaare Zedek Medical Center
Information provided by:	Shaare Zedek Medical Center
ClinicalTrials.gov Identifier:	NCT00616382

Purpose

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.

Condition	Intervention	Phase
Patent Ductus Arteriosus	Drug: Indomethacin Drug: Pentoxifylline	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	New Therapeutic Approaches to the Resistant Patent Ductus Arteriosus (PDA) in Low Birth Weight Neonates

Resource links provided by NLM:

Drug Information available for: Indomethacin Pentoxyl Pentoxifylline

U.S. FDA Resources

Further study details as provided by Shaare Zedek Medical Center:

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Our secondary objective is to compare the therapeutic efficacy of two very different secondary treatment protocols. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To monitor and compare potential side effects of the two treatment approaches [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	68
Study Start Date:	March 2008
Estimated Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Arms

Assigned Interventions

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

Eligibility

Ages Eligible for Study:	up to 4 Weeks
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00616382

Contacts

Contact: Cathy Hammerman, MD

9722 6666238

cathy@cc.huji.ac.il

Locations

Israel
Neonatal Intensive Care Unit - Shaare Zedek Medical Center	Not yet recruiting
Jerusalem, Israel, 91031
Principal Investigator: Cathy Hammerman, MD
Sub-Investigator: Irina Schorrs, MD
Sub-Investigator: Amiram Nir, MD

Sponsors and Collaborators

Shaare Zedek Medical Center

Investigators

Principal Investigator:

Cathy Hammerman, MD

Shaare Zedek Medical Center

More Information

Publications:

Sperandio M, Beedgen B, Feneberg R, Huppertz C, Brüssau J, Pöschl 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.

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.

Responsible Party:	Cathy Hammerman, Shaare Zedek Medical Center
ClinicalTrials.gov Identifier:	NCT00616382 History of Changes
Other Study ID Numbers:	CHPDA2
Study First Received:	January 13, 2008
Last Updated:	February 14, 2008
Health Authority:	Israel: Ministry of Health

Keywords provided by Shaare Zedek Medical Center:

PDA
indomethacin
pentoxifylline
Patent Ductus Arteriosus [PDA] resistant to therapy

Additional relevant MeSH terms:

Ductus Arteriosus, Patent
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Indomethacin
Pentoxifylline
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Tocolytic Agents
Reproductive Control Agents
Physiological Effects of Drugs

Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Cardiovascular Agents
Central Nervous System Agents
Phosphodiesterase Inhibitors
Platelet Aggregation Inhibitors
Hematologic Agents
Radiation-Protective Agents

ClinicalTrials.gov processed this record on February 09, 2012