Official Title: “Trial of Indomethacin Prophylaxis in Preterm Infants (TIPP)”

This trial will determine whether giving low-dose indomethacin to infants weight 500 to 999 grams (approximately 1 to 2 pounds) at birth improves their survival without cerebral palsy or developmental problems at 18 to 22 months of age.

Study Type: Interventional

Study Design: Prevention, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Efficacy Study

Prophylactic indomethacin reduces patent ductus arteriosus (PDA) and intraventricular hemorrhage in very low birth weight infants. However, the effects of early indomethacin on long-term neurodevelopment remain uncertain. There is also insufficient evidence to rule out serious adverse effects, such as increases in the risk of necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). The aim of this trial was to determine if prophylactic administration of indomethacin improves survival without neurosensory impairments in extremely-low-birth-weight infants. Infants (n=1202) with birthweights 500 to 999 grams were randomized between 2 and 6 hours after birth to receive either intravenous indomethacin (0.1 mg/kg) or equal volumes of normal saline placebo, daily for 3 days. The primary outcomes at a corrected age of 18 months was a composite of death, cerebral palsy, cognitive delay, deafness, or blindness. Secondary long-term outcomes were hydrocephalus necessitating the placement of a shunt, seizure disorder, and microcephaly. Secondary short-term outcomes were patent ductus arteriosus, pulmonary hemorrhage, chronic lung disease, cranial ultrasonographic abnormalities, nectrotizing enterocolitis and retinopathy. Infants were evaluated in follow-up at 18-22 months corrected age.

Intervention(s) in this Clinical Trial

• Drug: indomethacin

Inclusion Criteria:

• Birth weight 500 to 999 grams;
• Postnatal age greater than 2 hours;

Exclusion Criteria:

• Unable to administer study drug within 6 hours of birth;
• Structural heart disease and/or renal disease;
• Dysmorphic features or congenital abnormalities;
• Tocolytic therapy with indomethacin or other prostaglandin inhibitor within 72 hours prior to delivery;
• Overt clinical bleeding from more than one site;
• Platelet count less than 50 x 109/L;
• Hydrops;
• Not considered viable

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 6 Hours

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Overall Clinical Trial Officials and Contacts

Barbara Schmidt, MD Principal Investigator McMaster University  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00009646

Study ID Number: NICHD-1007

ClinicalTrials.gov Identifier: NCT00009646

Health Authority: United States: Food and Drug Administration

Click here for more information on NICHD clinical trials.

Click here for the Cochrane meta-analysis, "Prophylactic intravenous indomethacin in VLBW infants."