NCT00009620

Antenatal Phenobarbital to Prevent Neonatal Intracranial Hemorrhage

Randomized Clinical Trial of Antenatal Phenobarbital in the Prevention of Neonatal Intracranial Hemorrhage

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 610 (actual)
• Sponsor: NICHD Neonatal Research Network · Network
• Sex: Female
• Age: —
• Healthy volunteers: Accepted

Summary

This large randomized trial tested whether phenobarbital given to a pregnant woman about to deliver a premature infant would prevent brain injuries in their newborns. Women with 24 to 32 week fetuses who were in preterm labor and were expected to deliver within 24 hrs were randomized to phenobarbital or usual care. They were treated until they deliver or the fetus reaches 33 wks gestation. Babies were followed until discharge and evaluated at 18-22 mos corrected age for neurodevelopmental outcome.

Detailed description

The administration of phenobarbital to pregnant women before delivery has been thought to decrease the frequency of intracranial hemorrhage in preterm infants. To evaluate this potential neuroprotective therapy further, we determined the effect of antenatal administration of phenobarbital on the frequency of neonatal intracranial hemorrhage and early death. Women who were 24 to 33 weeks pregnant and who were expected to deliver their infants within 24 hours were randomly assigned to receive either intravenous phenobarbital (10 mg/kg body weight) or placebo, followed by maintenance doses until delivery or 34 wks gestation. Infants less than 34 wks at birth underwent serial cranial ultrasonography to detect the presence of intracranial hemorrhage. The sample size of 1038 pregnancies was based on an intracranial hemorrhage rate of 20 percent in the placebo and less than 12 percent in the phenobarbital group; 90 percent power; a 5 percent two-tailed type 1 error; and an 8 percent noncompliance rate. The twin with the highest grade of intracranial hemorrhage was included. Degree of maternal sedation was evaluated after administration of study drug. Neonatal ultrasound exams were performed at 3-5 days, 10-14 days, and 38-42 wks postmenstrual age; neonatal medications were recorded during the first week of life; treatments, and outcomes were recorded through death, discharge, or 120 days, whichever occurred first. Neurodevelopmental outcome was evaluated at 18-22 months corrected age by certified examiners masked to treatment status.

Conditions

• Infant, Newborn
• Infant, Low Birth Weight
• Infant, Small for Gestational Age
• Infant, Premature
• Intracranial Hemorrhages

Interventions

Type	Name	Description
DRUG	Phenobarbital	10 mg of phenobarbital per kilogram of body weight intravenously over a period of 20 to 40 minutes (maximal dose, 1000 mg)
DRUG	Saline	Infusion of normal sal

Timeline

• Start date: 1993-02-01
• Primary completion: 1995-02-01
• Completion: 1997-02-01
• First posted: 2001-02-05
• Last updated: 2019-03-22

Locations

11 sites across 1 country: United States