Infant, NewbornPhase 3PhenobarbitalNCT00009620
Antenatal Phenobarbital to Prevent Neonatal Intracranial Hemorrhage
A Phase 3 study testing Phenobarbital and Saline in people with Infant, Newborn and Infant, Low Birth Weight, run by NICHD Neonatal Research Network at 11 sites in United States.
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. Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age
- What is being tested?
- Phenobarbital and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 610 participants
- Where
- 11 sitesUnited States
- Study dates
- Feb 1993to Feb 1997
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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;
Who cannot join
- 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
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
University of New Mexico
Albuquerque, New Mexico, 87131
Emory University
Atlanta, Georgia, 30303
Cincinnati Children's Medical Center
Cincinnati, Ohio, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
Wayne State University
Detroit, Michigan, 48201
Indiana University
Indianapolis, Indiana, 46202
University of Tennessee
Memphis, Tennessee, 38163
Yale University
New Haven, Connecticut, 06504
Stanford University
Palo Alto, California, 94304
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
George Washington University
Washington D.C., District of Columbia, 20052
About this study
Official title: Randomized Clinical Trial of Antenatal Phenobarbital in the Prevention of Neonatal Intracranial Hemorrhage
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.
Read the 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.
- Conditions
- Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Intracranial Hemorrhages
- Being tested
- Phenobarbital, Saline
- 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
- Medical subject headings
- Premature Birth, Intracranial Hemorrhages, Cerebral Hemorrhage, Leukomalacia, Periventricular, Brain Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhenobarbitalDrug
10 mg of phenobarbital per kilogram of body weight intravenously over a period of 20 to 40 minutes (maximal dose, 1000 mg)
SalineDrug
Infusion of normal sal
| Study group | Role | What they receive |
|---|---|---|
| Phenobarbital | Experimental | Not described Receives: Drug: Phenobarbital |
| Placebo | Placebo comparator | Not described Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neonatal intracranial hemorrhage or death
Measured: 72 hours of life
Secondary outcomes (3)
Intracranial hemorrhage (grade I, II, III, or IV)
Measured: 72 hours of life
Periventricular leukomalacia
Measured: 72 hours of life
Neurodevelopmental impairment
Measured: 18 to 22 months of corrected age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2001 (estimated)
- Study startFeb 1993
- Primary completionFeb 1995
- Study completionFeb 1997
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Infant, NewbornStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 610 participants (actual)
Sponsor and investigators
- Lead sponsor
- NICHD Neonatal Research Network
- Sponsor type
- Research network
- Collaborators
- National Center for Research Resources (NCRR)
- Investigators
- Seetha Shankaran, MD, Study director, Wayne State UniversityLu-Ann Papile, MD, Principal investigator, University of New MexicoRichard A. Ehrenkranz, MD, Principal investigator, Yale UniversityRaymond Bain, PhD, Principal investigator, George Washington UniversityJames A. Lemons, MD, Principal investigator, Indiana UniversitySheldon B. Korones, MD, Principal investigator, University of Tennessee at MemphisDavid K. Stevenson, MD, Principal investigator, Stanford UniversityEdward F. Donovan, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00009620
- Sponsor's protocol ID
- NICHD-NRN-0006
- Other IDs
- U10HD021385, U10HD027881, U10HD027871, U01HD019897, U10HD027856, U10HD021415, U10HD027880, U10HD027853
- Acronym
- Phenobarbital
- Status last verified
- Mar 2019
- First submitted
- 1 Feb 2001
- Last updated
- 22 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 9250849McCain 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.
PubMed 10625862Shankaran 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.
PubMed 12114906
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Clinical Trial of Antenatal Phenobarbital in the Prevention of Neonatal Intracranial Hemorrhage
- ClinicalTrials.gov ID
- NCT00009620
- Acronym / sponsor ID
- Phenobarbital / NICHD-NRN-0006
- Conditions
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 610 participants (actual)
- Lead sponsor
- NICHD Neonatal Research NetworkResearch network
- Collaborators
- National Center for Research Resources (NCRR)
- Study start
- Feb 1993
- Primary completion
- Feb 1995 (actual)
- Study completion
- Feb 1997 (actual)
- First posted
- 5 Feb 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phenobarbital | Experimental | Drug: Phenobarbital |
| Placebo | Placebo comparator | Drug: Saline |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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;
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Phenobarbital10 mg of phenobarbital per kilogram of body weight intravenously over a period of 20 to 40 minutes (maximal dose, 1000 mg) | Drug | Phenobarbital |
| SalineInfusion of normal sal | Drug | Placebo |
Primary outcome
Neonatal intracranial hemorrhage or death
Time frame: 72 hours of life
3 secondary outcomes
Intracranial hemorrhage (grade I, II, III, or IV)
Time frame: 72 hours of life
Periventricular leukomalacia
Time frame: 72 hours of life
Neurodevelopmental impairment
Time frame: 18 to 22 months of corrected age
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2019.
- Results publication: PubMed 9250849Shankaran 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 publication: PubMed 10625862McCain 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.
- Results publication: PubMed 12114906Shankaran 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.
- NICHD Neonatal Research NetworkLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Seetha Shankaran, MD study director
Wayne State University
Lu-Ann Papile, MD principal investigator
University of New Mexico
Richard A. Ehrenkranz, MD principal investigator
Yale University
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Phenobarbital and Saline in people with Infant, Newborn and Infant, Low Birth Weight, run by NICHD Neonatal Research Network at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neonatal intracranial hemorrhage or death (time frame: 72 hours of life). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00009620, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2019.