Trial of Indomethacin Prophylaxis in Preterm Infants (TIPP)
Information source: National Institute of Child Health and Human Development (NICHD)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Infant, Very Low Birth Weight; Infant, Premature; Ductus Arteriosus, Patent
Intervention: indomethacin (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: National Institute of Child Health and Human Development (NICHD) Official(s) and/or principal investigator(s):
Barbara Schmidt, MD, Principal Investigator, Affiliation: Hamilton Health Sciences
Summary
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.
Clinical Details
Official title: Trial of Indomethacin Prophylaxis in Preterm Infants (TIPP)
Study design: Prevention, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Efficacy Study
Detailed 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.
Eligibility
Minimum age: N/A.
Maximum age: 6 Hours.
Gender(s): 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
Locations and Contacts
Additional Information
Click here for more information on NICHD clinical trials. Click here for the Cochrane meta-analysis, "Prophylactic intravenous indomethacin in VLBW infants."
Related publications: Schmidt B, Davis P, Moddemann D, Ohlsson A, Roberts RS, Saigal S, Solimano A, Vincer M, Wright LL. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med. 2001 Jun 28;344(26):1966-72. Schmidt B, Asztalos EV, Roberts RS, Robertson CM, Sauve RS, Whitfield MF. Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms. JAMA. 2003 Mar 5;289(9):1124-9.
Starting date: November 1993
Ending date: April 2000
Last updated: January 26, 2007
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