Trial | NCT00009646  Report issue

Official Title

Trial of Indomethacin Prophylaxis in Preterm Infants (TIPP)

  • Phase

    Phase 3

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Intervention/Treatment

    indomethacin ...

  • Study Participants

    1202
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.
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.
Study Started
Nov 30
1993
Primary Completion
Mar 31
1999
Study Completion
Mar 31
2001
Last Update
Jun 08
2015
Estimate

Drug indomethacin

Indocid P.D.A., Merck Frosst, Kirkland, Que., Canada, and Merck, West Point, Pa

Drug Indomethacin

0.1 mg per kilogram of body weight

Drug Placebo

0.1 mg per kilogram of body weight

Indomethacin Experimental

Indocid P.D.A., Merck Frosst, Kirkland, Que., Canada, and Merck, West Point, Pa.

Placebo Placebo Comparator

Saline solution

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
No Results Posted