Antenatal Phenobarbital to Prevent Neonatal Intracranial Hemorrhage

Infant, Premature Clinical Trial

— Phenobarbital  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00009620
• Other study ID #: NICHD-NRN-0006
• Secondary ID: U10HD021385U10HD
• Status: Completed
• Phase: Phase 3
• Start date: February 1993
• Est. completion date: February 1997

Study information

• Verified date: March 2019
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 610
• Est. completion date: February 1997
• Est. primary completion date: February 1995
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Phenobarbital
10 mg of phenobarbital per kilogram of body weight intravenously over a period of 20 to 40 minutes (maximal dose, 1000 mg)
• Saline
Infusion of normal sal

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	Cincinnati Children's Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Wayne State University	Detroit	Michigan
United States	Indiana University	Indianapolis	Indiana
United States	University of Tennessee	Memphis	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Stanford University	Palo Alto	California
United States	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island
United States	George Washington University	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

References & Publications (3)

McCain GC, Donovan EF, Gartside P. Preterm infant behavioral and heart rate responses to antenatal phenobarbital. Res Nurs Health. 1999 Dec;22(6):461-70. Erratum in: Res Nurs Health 2000 Aug;23(4):341. — View Citation

Shankaran S, Papile LA, Wright LL, Ehrenkranz RA, Mele L, Lemons JA, Korones SB, Stevenson DK, Donovan EF, Stoll BJ, Fanaroff AA, Oh W, Verter J. Neurodevelopmental outcome of premature infants after antenatal phenobarbital exposure. Am J Obstet Gynecol. — View Citation

Shankaran S, Papile LA, Wright LL, Ehrenkranz RA, Mele L, Lemons JA, Korones SB, Stevenson DK, Donovan EF, Stoll BJ, Fanaroff AA, Oh W. The effect of antenatal phenobarbital therapy on neonatal intracranial hemorrhage in preterm infants. N Engl J Med. 199 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neonatal intracranial hemorrhage or death		72 hours of life
Secondary	Intracranial hemorrhage (grade I, II, III, or IV)		72 hours of life
Secondary	Periventricular leukomalacia		72 hours of life
Secondary	Neurodevelopmental impairment		18 to 22 months of corrected age

External Links

•   NICHD Neonatal Research Network