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Antenatal Phenobarbital to Prevent Neonatal Intracranial Hemorrhage (Phenobarbital)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00009620
Recruitment Status : Completed
First Posted : February 5, 2001
Last Update Posted : March 22, 2019
National Center for Research Resources (NCRR)
Information provided by:
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.

Condition or disease Intervention/treatment Phase
Infant, Newborn Infant, Low Birth Weight Infant, Small for Gestational Age Infant, Premature Intracranial Hemorrhages Drug: Phenobarbital Drug: Saline Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 610 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Prevention
Official Title: Randomized Clinical Trial of Antenatal Phenobarbital in the Prevention of Neonatal Intracranial Hemorrhage
Study Start Date : February 1993
Actual Primary Completion Date : February 1995
Actual Study Completion Date : February 1997

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Arm Intervention/treatment
Experimental: Phenobarbital Drug: Phenobarbital
10 mg of phenobarbital per kilogram of body weight intravenously over a period of 20 to 40 minutes (maximal dose, 1000 mg)

Placebo Comparator: Placebo Drug: Saline
Infusion of normal sal

Primary Outcome Measures :
  1. Neonatal intracranial hemorrhage or death [ Time Frame: 72 hours of life ]

Secondary Outcome Measures :
  1. Intracranial hemorrhage (grade I, II, III, or IV) [ Time Frame: 72 hours of life ]
  2. Periventricular leukomalacia [ Time Frame: 72 hours of life ]
  3. Neurodevelopmental impairment [ Time Frame: 18 to 22 months of corrected age ]

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00009620

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United States, California
Stanford University
Palo Alto, California, United States, 94304
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06504
United States, District of Columbia
George Washington University
Washington, District of Columbia, United States, 20052
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30303
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, Ohio
Cincinnati Children's Medical Center
Cincinnati, Ohio, United States, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, United States, 02905
United States, Tennessee
University of Tennessee
Memphis, Tennessee, United States, 38163
Sponsors and Collaborators
NICHD Neonatal Research Network
National Center for Research Resources (NCRR)
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Study Director: Seetha Shankaran, MD Wayne State University
Principal Investigator: Lu-Ann Papile, MD University of New Mexico
Principal Investigator: Richard A. Ehrenkranz, MD Yale University
Principal Investigator: Raymond Bain, PhD George Washington University
Principal Investigator: James A. Lemons, MD Indiana University
Principal Investigator: Sheldon B. Korones, MD University of Tennessee at Memphis
Principal Investigator: David K. Stevenson, MD Stanford University
Principal Investigator: Edward F. Donovan, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Barbara J. Stoll, MD Emory University
Principal Investigator: Avroy A. Fanaroff, MD Case Western Reserve University
Principal Investigator: William Oh, MD Brown University, Women and Infants Hospital
Additional Information:
Publications of Results:
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Responsible Party: Seetha Shankaran/ Lead Principal Investigator, Wayne State University Identifier: NCT00009620    
Other Study ID Numbers: NICHD-NRN-0006
U10HD021385 ( U.S. NIH Grant/Contract )
U10HD027881 ( U.S. NIH Grant/Contract )
U10HD027871 ( U.S. NIH Grant/Contract )
U01HD019897 ( U.S. NIH Grant/Contract )
U10HD027856 ( U.S. NIH Grant/Contract )
U10HD021415 ( U.S. NIH Grant/Contract )
U10HD027880 ( U.S. NIH Grant/Contract )
U10HD027853 ( U.S. NIH Grant/Contract )
U10HD027851 ( U.S. NIH Grant/Contract )
U10HD021364 ( U.S. NIH Grant/Contract )
U10HD027904 ( U.S. NIH Grant/Contract )
M01RR000997 ( U.S. NIH Grant/Contract )
M01RR006022 ( U.S. NIH Grant/Contract )
M01RR000750 ( U.S. NIH Grant/Contract )
M01RR000070 ( U.S. NIH Grant/Contract )
M01RR008084 ( U.S. NIH Grant/Contract )
First Posted: February 5, 2001    Key Record Dates
Last Update Posted: March 22, 2019
Last Verified: March 2019
Keywords provided by NICHD Neonatal Research Network:
NICHD Neonatal Research Network
Extremely Low Birth Weight (ELBW)
Cerebral hemorrhage
Prenatal care
Intraventricular hemorrhage
Periventricular leukomalacia
Brain injury
Brain hemorrhage
Additional relevant MeSH terms:
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Intracranial Hemorrhages
Birth Weight
Pathologic Processes
Body Weight
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
GABA Modulators
GABA Agents
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers