Brief Title
Comparison of 2 Different Indomethacin Dosing Protocols to Treat Infants Delivered at <28 Weeks Gestation With a Persistent Patent Ductus Arteriosus
Official Title
Comparison of 2 Different Indomethacin Dosing Protocols to Treat Infants Delivered at <28 Weeks Gestation With a Persistent Patent Ductus Arteriosus
Brief 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.
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
The incidence of ductus closure, as determined by echocardiography, following the last dose of study drug
Secondary Outcome
Altered renal function during treatment
Condition
Patent Ductus Arteriosus
Intervention
indomethacin (two different dosing regimens)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
100
Start Date
August 2003
Completion Date
July 2006
Primary Completion Date
July 2006
Eligibility Criteria
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).
Gender
All
Ages
N/A - 48 Hours
Accepts Healthy Volunteers
No
Contacts
Ronald Clyman, M.D., ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00187447
Organization ID
RC1
Study Sponsor
University of California, San Francisco
Study Sponsor
Ronald Clyman, M.D., Principal Investigator, University of California, San Francisco
Verification Date
September 2005