Clinical Trial: Antenatal Phenobarbital to Prevent Neonatal Intracranial Hemorrhage
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Randomized Clinical Trial of Antenatal Phenobarbital in the Prevention of Neonatal Intracranial Hemorrhage
Brief 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 Summary:
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.
Sponsor: NICHD Neonatal Research Network
Current Primary Outcome: Neonatal intracranial hemorrhage or death [ Time Frame: 72 hours of life ]
Original Primary Outcome:
Current Secondary Outcome:
- Intracranial hemorrhage (grade I, II, III, or IV) [ Time Frame: 72 hours of life ]
- Periventricular leukomalacia [ Time Frame: 72 hours of life ]
- Neurodevelopmental impairment [ Time Frame: 18 to 22 months of corrected age ]
Original Secondary Outcome:
Information By: NICHD Neonatal Research Network
Dates:
Date Received: February 1, 2001
Date Started: February 1993
Date Completion:
Last Updated: June 3, 2015
Last Verified: June 2015
