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Antenatal Phenobarbital to Prevent Neonatal Intracranial Hemorrhage (Phenobarbital)

Primary Purpose

Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Phenobarbital
Saline
Sponsored by
NICHD Neonatal Research Network
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Infant, Newborn focused on measuring NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Prematurity, Cerebral hemorrhage, Phenobarbital, Pregnancy, Prenatal care, Intraventricular hemorrhage, Periventricular leukomalacia, Brain injury, Brain hemorrhage

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)FemaleAccepts Healthy Volunteers

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

Sites / Locations

  • Stanford University
  • Yale University
  • George Washington University
  • Emory University
  • Indiana University
  • Wayne State University
  • University of New Mexico
  • Cincinnati Children's Medical Center
  • Case Western Reserve University, Rainbow Babies and Children's Hospital
  • Brown University, Women & Infants Hospital of Rhode Island
  • University of Tennessee

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Phenobarbital

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Neonatal intracranial hemorrhage or death

Secondary Outcome Measures

Intracranial hemorrhage (grade I, II, III, or IV)
Periventricular leukomalacia
Neurodevelopmental impairment

Full Information

First Posted
February 1, 2001
Last Updated
March 20, 2019
Sponsor
NICHD Neonatal Research Network
Collaborators
National Center for Research Resources (NCRR)
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1. Study Identification

Unique Protocol Identification Number
NCT00009620
Brief Title
Antenatal Phenobarbital to Prevent Neonatal Intracranial Hemorrhage
Acronym
Phenobarbital
Official Title
Randomized Clinical Trial of Antenatal Phenobarbital in the Prevention of Neonatal Intracranial Hemorrhage
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
February 1993 (undefined)
Primary Completion Date
February 1995 (Actual)
Study Completion Date
February 1997 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
NICHD Neonatal Research Network
Collaborators
National Center for Research Resources (NCRR)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Intracranial Hemorrhages
Keywords
NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Prematurity, Cerebral hemorrhage, Phenobarbital, Pregnancy, Prenatal care, Intraventricular hemorrhage, Periventricular leukomalacia, Brain injury, Brain hemorrhage

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
610 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phenobarbital
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Phenobarbital
Intervention Description
10 mg of phenobarbital per kilogram of body weight intravenously over a period of 20 to 40 minutes (maximal dose, 1000 mg)
Intervention Type
Drug
Intervention Name(s)
Saline
Intervention Description
Infusion of normal sal
Primary Outcome Measure Information:
Title
Neonatal intracranial hemorrhage or death
Time Frame
72 hours of life
Secondary Outcome Measure Information:
Title
Intracranial hemorrhage (grade I, II, III, or IV)
Time Frame
72 hours of life
Title
Periventricular leukomalacia
Time Frame
72 hours of life
Title
Neurodevelopmental impairment
Time Frame
18 to 22 months of corrected age

10. Eligibility

Sex
Female
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Seetha Shankaran, MD
Organizational Affiliation
Wayne State University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Lu-Ann Papile, MD
Organizational Affiliation
University of New Mexico
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Richard A. Ehrenkranz, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Raymond Bain, PhD
Organizational Affiliation
George Washington University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
James A. Lemons, MD
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sheldon B. Korones, MD
Organizational Affiliation
University of Tennessee at Memphis
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David K. Stevenson, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Edward F. Donovan, MD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Barbara J. Stoll, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Avroy A. Fanaroff, MD
Organizational Affiliation
Case Western Reserve University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
William Oh, MD
Organizational Affiliation
Brown University, Women and Infants Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06504
Country
United States
Facility Name
George Washington University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20052
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of New Mexico
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Cincinnati Children's Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Case Western Reserve University, Rainbow Babies and Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Brown University, Women & Infants Hospital of Rhode Island
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Facility Name
University of Tennessee
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38163
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
9250849
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. 1997 Aug 14;337(7):466-71. doi: 10.1056/NEJM199708143370705.
Results Reference
result
PubMed Identifier
10625862
Citation
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. doi: 10.1002/(sici)1098-240x(199912)22:63.0.co;2-t. Erratum In: Res Nurs Health 2000 Aug;23(4):341.
Results Reference
result
PubMed Identifier
12114906
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. 2002 Jul;187(1):171-7. doi: 10.1067/mob.2002.122445.
Results Reference
result
Links:
URL
http://neonatal.rti.org/
Description
NICHD Neonatal Research Network

Learn more about this trial

Antenatal Phenobarbital to Prevent Neonatal Intracranial Hemorrhage

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