Ductus Arteriosus, Patent, Infant, Premature, Infant, Very Low Birth Weight
Conditions
Keywords
Chronic lung disease, Indocin, Indomethacin, Infants, very low birth weight, Intraventricular hemorrhage, Necrotizing enterocolitis, Patent ductus arteriosus, Pulmonary hemorrhage
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.
Interventions
DRUGindomethacin
Indocid P.D.A., Merck Frosst, Kirkland, Que., Canada, and Merck, West Point, Pa
DRUGIndomethacin
0.1 mg per kilogram of body weight
DRUGPlacebo
0.1 mg per kilogram of body weight
Sponsors
Medical Research Council of Canada
National Center for Research Resources (NCRR)
NICHD Neonatal Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Hours to 6 Hours
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Death or Neurodevelopment Impairment | 18-22 Months Corrected Age |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary hemorrhage | 120 Days of Life | — |
| Retinopathy of Prematurity (ROP) | 18-22 Months Corrected Age | — |
| Bronchopulmonary Dysplasia (BPD) | 120 Days of Life | Chronic Lung Disease (CLD) |
| Necrotizing enterocolitis (NEC) | 120 Days of Life | — |
| Intracranial abnormalities | 120 Days of Life | — |
| Patent ductus arteriosus | 120 Days of Life | — |
Countries
United States
Outcome results
None listed