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

Patent Ductus Arteriosus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00187447
• Other study ID #: RC1
• Status: Completed
• Phase: Phase 2
• First received: September 10, 2005
• Last updated: June 2, 2008
• Start date: August 2003
• Est. completion date: July 2006

Study information

• Verified date: September 2005
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: July 2006
• Est. primary completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 48 Hours

Eligibility

Inclusion Criteria:

1. Newborn infants of less than 28 weeks gestational age who are treated with indomethacin during the first 48 hours after birth

2. Presence of patent ductus arteriosus (PDA) by Doppler echocardiography between the second and third dose of indomethacin.

3. Creatinine =1.8 mg/dl

4. Platelets = 50,000

Exclusion Criteria:

1. Chromosomal disorders.

2. Major congenital anomalies.

3. 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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Ductus Arteriosus, Patent
• Patent Ductus Arteriosus

Intervention

Drug:
• indomethacin (two different dosing regimens)

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois
United States	University of California San Francisco	Davis	California
United States	Brown University	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of ductus closure, as determined by echocardiography, following the last dose of study drug
Primary	The incidence of the appearance of a symptomatic PDA following the last dose of study drug
Primary	The incidence of ductus ligation.
Secondary	Altered renal function during treatment
Secondary	Incidence of Necrotizing enterocolitis
Secondary	Incidence of chronic lung disease