Trial of Indomethacin Prophylaxis in Preterm Infants (TIPP)
- Conditions
- Infant, Very Low Birth WeightInfant, PrematureDuctus Arteriosus, Patent
- Interventions
- Drug: Placebo
- Registration Number
- NCT00009646
- Lead Sponsor
- NICHD Neonatal Research Network
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1202
- Birth weight 500 to 999 grams;
- Postnatal age greater than 2 hours;
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Saline solution Indomethacin Indomethacin Indocid P.D.A., Merck Frosst, Kirkland, Que., Canada, and Merck, West Point, Pa.
- Primary Outcome Measures
Name Time Method Death or Neurodevelopment Impairment 18-22 Months Corrected Age
- Secondary Outcome Measures
Name Time Method Patent ductus arteriosus 120 Days of Life Pulmonary hemorrhage 120 Days of Life Bronchopulmonary Dysplasia (BPD) 120 Days of Life Chronic Lung Disease (CLD)
Necrotizing enterocolitis (NEC) 120 Days of Life Intracranial abnormalities 120 Days of Life Retinopathy of Prematurity (ROP) 18-22 Months Corrected Age
Trial Locations
- Locations (9)
University of Texas Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Brown University, Women & Infants Hospital of Rhode Island
🇺🇸Providence, Rhode Island, United States
University of Miami
🇺🇸Miami, Florida, United States
Stanford University
🇺🇸Palo Alto, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Case Western Reserve University, Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States