Antenatal Phenobarbital to Prevent Neonatal Intracranial Hemorrhage

Phase 3

Completed

• Conditions: Infant, Newborn; Infant, Low Birth Weight; Intracranial Hemorrhages; Infant, Small for Gestational Age; Infant, Premature
• Interventions: Drug: Phenobarbital; Drug: Saline

• Registration Number: NCT00009620
• Lead Sponsor: NICHD Neonatal Research Network

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 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.

Study Timeline

• Study Start: 1993-02
• Primary Completion: 1995-02
• Study Completion: 1997-02
• Study First Submitted: 2001-02-01
• Study First Submitted QC: 2001-02-02
• Study First Posted: 2001-02-05
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-20
• Last Update Posted: 2019-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 610

Inclusion Criteria

• Admission to a high risk perinatal unit or labor and delivery unit;
• 24 to 32 completed weeks gestation;
• Expected delivery within 24 hrs;
• Preterm labor or no labor with planned delivery for maternal-fetal indications;

Exclusion Criteria

• Anticipated delivery within two hours
• Multiple congenital or chromosomal abnormalities in the fetus
• Multiple gestation with more than two fetuses
• Administration of phenobarbital during the pregnancy
• Administration of indomethacin within one week before admission
• Maternal platelet count of less than 100,000 per cubic millimeter

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phenobarbital	Phenobarbital	-
Placebo	Saline	-

Primary Outcome Measures

Name	Time	Method
Neonatal intracranial hemorrhage or death	72 hours of life

Secondary Outcome Measures

Name	Time	Method
Intracranial hemorrhage (grade I, II, III, or IV)	72 hours of life
Periventricular leukomalacia	72 hours of life
Neurodevelopmental impairment	18 to 22 months of corrected age

Trial Locations

Locations (11)

Yale University; 🇺🇸 New Haven, Connecticut, United States

George Washington University; 🇺🇸 Washington, District of Columbia, United States

University of New Mexico; 🇺🇸 Albuquerque, New Mexico, United States

University of Tennessee; 🇺🇸 Memphis, Tennessee, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

Wayne State University; 🇺🇸 Detroit, Michigan, United States

Case Western Reserve University, Rainbow Babies and Children's Hospital; 🇺🇸 Cleveland, Ohio, United States

Cincinnati Children's Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Brown University, Women & Infants Hospital of Rhode Island; 🇺🇸 Providence, Rhode Island, United States