Trial of Indomethacin Prophylaxis in Preterm Infants (TIPP)

NICHD Neonatal Research Network

Status and phase

Completed

Phase 3

Conditions

Ductus Arteriosus, Patent

Infant, Very Low Birth Weight

Infant, Premature

Treatments

Drug: Placebo

Drug: indomethacin

Drug: Indomethacin

Study type

Interventional

Funder types

Other

NETWORK

NIH

Identifiers

NCT00009646

M01RR000997 (U.S. NIH Grant/Contract)

U10HD021373 (U.S. NIH Grant/Contract)

NICHD-NRN-0011

M01RR000070 (U.S. NIH Grant/Contract)

U10HD021364 (U.S. NIH Grant/Contract)

U10HD027880 (U.S. NIH Grant/Contract)

U10HD027851 (U.S. NIH Grant/Contract)

U10HD027881 (U.S. NIH Grant/Contract)

U10HD021397 (U.S. NIH Grant/Contract)

MT-13288 (Other Grant/Funding Number)

U10HD034216 (U.S. NIH Grant/Contract)

U10HD021385 (U.S. NIH Grant/Contract)

U10HD027904 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This trial was to 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.

Full description

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.

Enrollment

1,202 patients

Sex

All

Ages

2 to 6 hours old

Volunteers

No Healthy Volunteers

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