Comparison of 2 Different Indomethacin Dosing Protocols to Treat Infants Delivered at <28 Weeks Gestation With a Persistent Patent Ductus Arteriosus - Full Text View

Sponsored by:	University of California, San Francisco
Information provided by:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00187447

Purpose

The purpose of this study is to examine if a higher dose of indomethacin will increase the rate of ductus arteriosus closure in extremely premature infants without increasing the side effects. The long term objective is to find the optimal dosing of indomethacin for permanent closure of the Ductus and prevent the morbidity related to PDA and the complications of surgical ligation.

Condition	Intervention	Phase
Patent Ductus Arteriosus	Drug: indomethacin (two different dosing regimens)	Phase II

Drug Information available for: Indomethacin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double-Blind, Dose Comparison, Single Group Assignment, Safety/Efficacy Study
Official Title:	Comparison of 2 Different Indomethacin Dosing Protocols to Treat Infants Delivered at <28 Weeks Gestation With a Persistent Patent Ductus Arteriosus

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:

The incidence of ductus closure, as determined by echocardiography, following the last dose of study drug
The incidence of the appearance of a symptomatic PDA following the last dose of study drug
The incidence of ductus ligation.

Secondary Outcome Measures:

Altered renal function during treatment
Incidence of Necrotizing enterocolitis
Incidence of chronic lung disease

Estimated Enrollment:	100
Study Start Date:	August 2003
Study Completion Date:	July 2006
Primary Completion Date:	July 2006 (Final data collection date for primary outcome measure)

Detailed Description:

This study is a Phase II randomized, masked, controlled trial that compares the current standard dose of indomethacin to a higher dose for the closure of PDA in premature infants less than 28 weeks of gestation.

Neonates (<28 weeks gestation) who are started on indomethacin treatment (with an initial 3-dose course: 0.2, 0.1, and 0.1 mg/kg of indomethacin) within the first 96 hr after birth will be eligible for this trial if they continue to have Doppler evidence of ductus patency before the third dose of indomethacin. This group of infants have greater than 65% chance of developing symptomatic PDA and surgical ligation even after our standard extended course of indomethacin. Those infants who do not fit the exclusion criteria will be randomized to either a Standard Dose group or to a Higher Dose group after obtaining consent. The infants randomized to the standard group will receive a 4th, 5th, and 6th dose of indomethacin (0.1 mg/kg) at 24 hr intervals (starting at 24 hr after the 3rd dose). The Higher Dose group infants delivered between 26-27 weeks gestation will receive a 4th, 5th, 6th, 7th, 8th and 9th dose of indomethacin (0.1mg/kg) at 12 hr intervals (starting 12 hr after the 3rd dose). The Higher Dose group infants between 24-25 weeks gestation will receive a 4th, 5th, 6th, 7th, 8th and 9th dose of indomethacin (0.25mg/kg) at 12 hour intervals (starting 12 hr after the 3rd dose). To keep the study blinded, the standard group will receive 3 extra doses of saline to match the 3 additional doses given to the higher dose group.

Eligibility

Ages Eligible for Study:	up to 48 Hours
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Newborn infants of less than 28 weeks gestational age who are treated with indomethacin during the first 48 hours after birth
Presence of patent ductus arteriosus (PDA) by Doppler echocardiography between the second and third dose of indomethacin.
Creatinine ≤1.8 mg/dl
Platelets ≥ 50,000

Exclusion Criteria:

Chromosomal disorders.
Major congenital anomalies.
Contraindications for indomethacin
1. Necrotizing enterocolitis, by clinical or radiological evidence
2. Evidence of bleeding diathesis as evidenced by pulmonary hemorrhage, persistent oozing from puncture sites, grossly bloody stool (Note: Infants with an intracranial hemorrhage can be enrolled in this study).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00187447

Locations

United States, California
University of California San Francisco
Davis, California, United States, 94143
United States, Illinois
University of Chicago
Chicago, Illinois, United States
United States, Rhode Island
Brown University
Providence, Rhode Island, United States

Sponsors and Collaborators

University of California, San Francisco

Investigators

Principal Investigator:

Ronald Clyman, M.D.

University of California, San Francisco

More Information

Study ID Numbers:	RC1
Study First Received:	September 10, 2005
Last Updated:	June 2, 2008
ClinicalTrials.gov Identifier:	NCT00187447
Health Authority:	United States: Institutional Review Board

Keywords provided by University of California, San Francisco:

prematurity
chronic lung disease
necrotizing enterocolitis
indomethacin
ductus arteriosus

Study placed in the following topic categories:

Heart Diseases
Cardiovascular Abnormalities
Lung Diseases
Indomethacin
Necrotizing enterocolitis
Patent ductus arteriosus

Congenital Abnormalities
Enterocolitis, Necrotizing
Heart Defects, Congenital
Enterocolitis
Ductus Arteriosus, Patent

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Cardiovascular Agents
Reproductive Control Agents
Gout Suppressants
Pharmacologic Actions
Tocolytic Agents

Sensory System Agents
Analgesics, Non-Narcotic
Therapeutic Uses
Cardiovascular Diseases
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 15, 2009