Antenatal Phenobarbital to Prevent Neonatal Intracranial Hemorrhage

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00009620
First received: February 1, 2001
Last updated: January 9, 2011
Last verified: January 2001
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: Randomized Clinical Trial of Antenatal Phenobarbital in the Prevention of Neonatal Intracranial Hemorrhage

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Neonatal intracranial hemorrhage or death [ Time Frame: 72 hours of life ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Intracranial hemorrhage (grade I, II, III, or IV) [ Time Frame: 72 hours of life ] [ Designated as safety issue: Yes ]
  • Periventricular leukomalacia [ Time Frame: 72 hours of life ] [ Designated as safety issue: Yes ]
  • Neurodevelopmental impairment [ Time Frame: 18 to 22 months of corrected age ] [ Designated as safety issue: Yes ]

Enrollment: 610
Study Start Date: February 1993
Study Completion Date: February 1997
Primary Completion Date: February 1995 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00009620

Locations
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
Investigators
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 Cincinnati Children's Medical Center
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
  More Information

Additional Information:
Publications:
Responsible Party: Seetha Shankaran/ Lead Principal Investigator, Wayne State University
ClinicalTrials.gov Identifier: NCT00009620     History of Changes
Other Study ID Numbers: NICHD-NRN-0006, U10HD021385, U10HD027881, U10HD027871, U01HD019897, U10HD027856, U10HD021415, U10HD027880, U10HD027853, U10HD027851, U10HD021364, U10HD027904, M01RR000997, M01RR006022, M01RR000750, M01RR000070, M01RR008084
Study First Received: February 1, 2001
Last Updated: January 9, 2011
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
NICHD Neonatal Research Network
Pregnancy
Extremely Low Birth Weight (ELBW)
Prematurity
Cerebral hemorrhage
Phenobarbital
Prenatal care
Intraventricular hemorrhage
Periventricular leukomalacia
Brain injury
Brain hemorrhage

Additional relevant MeSH terms:
Birth Weight
Hemorrhage
Intracranial Hemorrhages
Body Weight
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Nervous System Diseases
Pathologic Processes
Signs and Symptoms
Vascular Diseases
Phenobarbital
Anticonvulsants
Central Nervous System Agents
Central Nervous System Depressants
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
GABA Agents
GABA Modulators
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014