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.

Condition	Treatment or Intervention	Phase
Infant, very low birth weight Infant, Premature Ductus Arteriosus, Patent	Drug: indomethacin	Phase III

Further Study Details: 

Expected Total Enrollment:  1202

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.

Ages Eligible for Study:  up to  6 Hours,  Genders Eligible for Study:  Both

Criteria

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

Study chairs or principal investigators

Barbara Schmidt, MD,  Principal Investigator,  McMaster University   

Study ID Numbers:  NICHD-1007; U10 HD34216; U10 HD27904; U10 HD21364; U10 HD27851; U10 HD21397; U10 HD27881; U10 HD27880; U10 HD21373; U10 HD21385
Record last reviewed:  January 2001
Last Updated:  October 13, 2004
Record first received:  February 1, 2001
ClinicalTrials.gov Identifier:  NCT00009646
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08