Neonatal SeizuresPhase 4PROPHENONCT01089504
Prophylactic Phenobarbital After Neonatal Seizures
A Phase 4 study testing phenobarbital in people with Neonatal Seizures, run by University of Rochester at 18 sites in United States.
Trial summary
The treatment of infants with medications after their seizures have stopped is very variable. No one knows if continuing treatment with phenobarbital for up to several months is helpful or harmful. Read more about this study
- Who is it for?
- Ages 2 days to 2 weeks
- Conditions the study is for
- Neonatal Seizures
- What is being tested?
- phenobarbital
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 18 sitesUnited States
- Study dates
- Sep 2010to Nov 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 2 days to 2 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Birth at > 34 weeks' gestation
- Neonatal seizures (clinical, electrographic or both), with onset in the first 120 hours after birth and resolution within 7 days of onset
- Parental informed consent
Who cannot join
- Birth at < 34 weeks' gestation
- If the attending neonatologist attributes the seizures solely to a transient abnormality, easily correctable and unlikely to recur (eg, transient electrolyte abnormalities). If the attending neonatologist cannot be contacted, the site PI will be asked to review the available information and judge whether the infant is eligible.
- If the infant has been diagnosed with or there is a strong suspicion of an inborn error of metabolism, significant brain malformation, microcephaly (< 3 %ile), or a chromosomal abnormality which, in the absence of seizures, is known to be independently associated with an increased likelihood of cognitive impairment
- If the infant has been diagnosed with an intrauterine viral infection
- If the infant is not expected to survive to discharge
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
Akron Children's Hospital
Akron, Ohio, 44308
University of Michigan
Ann Arbor, Michigan, 48109
Johns Hopkins University
Baltimore, Maryland, 21224
Tufts Medical Center
Boston, Massachusetts, 02111
Women & Children's Hospital of Buffalo
Buffalo, New York, 14222
University of Virginia
Charlottesville, Virginia, 22908
Nationwide Children's Hospital
Columbus, Ohio, 43205
Univeristy of Iowa
Iowa City, Iowa, 52242
University of Arkansas
Little Rock, Arkansas, 72202
Magee Womens Hospital
Pittsburgh, Pennsylvania, 15224
University of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Women & Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
University of Rochester
Rochester, New York, 14642
Primary Children's Medical Center
Salt Lake City, Utah, 84108
University of Utah
Salt Lake City, Utah, 84108
University of California San Francisco
San Francisco, California, 94143
Forsyth Medical Center
Winston-Salem, North Carolina, 27157
Wake Forest University
Winston-Salem, North Carolina, 27157
About this study
Official title: Prophylactic Phenobarbital After Resolution of Neonatal Seizures
The treatment of infants with medications after their seizures have stopped is very variable. No one knows if continuing treatment with phenobarbital for up to several months is helpful or harmful. This clinical trial is designed to help answer that question and provide data that will help determine standard of care for these children.
Read the detailed description
The treatment of infants with antiepileptic medications after the resolution of neonatal seizures is highly variable and controversial. Infants are commonly treated with phenobarbital after their seizures have resolved to prevent recurrence. Data to support this practice are lacking but animal models suggest that the neonatal brain is vulnerable to repeated seizures. Yet exposure of the developing brain to phenobarbital for prolonged periods may have deleterious consequences. We are proposing a multi-center, randomized, clinical trial (RCT) to determine if continued treatment with phenobarbital reduces seizure recurrence without adversely affecting neurodevelopmental outcome or if infants' outcomes are improved if no prophylactic medication is given. We will identify infants with seizures beginning in the first week that resolve within 7 days and randomize them to receive phenobarbital or placebo daily for four months. Via visits and frequent telephone contacts over the first six months, we will determine the rate of seizure recurrence. The primary outcome, neurodevelopmental status, will be assessed at 18-22 months using the Bayley Scales of Infant Development. Additional subgroup analyses are planned to determine the contribution of seizure etiology to outcome and predictive value of initial EEG classification. The trial will be conducted at 18 - 20 sites, chosen for their experience and proven track record for enrollment and retention in this specific population. The trial will be coordinated by the Clinical Trials Coordination Center at the University of Rochester and overseen by a Steering Committee composed of experienced trialists representing neonatology and pediatric neurology, biostatistics, and clinical trial administration.
Extrapolation from the results of an RCT of phenobarbital prophylaxis after febrile seizures in children suggests that phenobarbital may adversely affect brain development and may be ineffective in preventing seizures. Based on this previous RCT that resulted in near universal change in practice (the elimination of prolonged use of phenobarbital after simple febrile seizures), we anticipate that the data we generate may have a similar impact on standard of care for infants with neonatal seizures.
- Conditions
- Neonatal Seizures
- Being tested
- phenobarbital, placebo
- Keywords
- phenobarbital, neonate, antiepileptic drugs, neurodevelopmental outcome, seizure
- Medical subject headings
- Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
phenobarbitalDrug
Phenobarbital, 4-5 mg/kg/d, by mouth, for 4 months
placeboDrug
Matched placebo, same volume as active drug, by mouth daily for 4 months
| Study group | Role | What they receive |
|---|---|---|
| Phenobarbital | Active comparator | Phenobarbital, 4-5 mg/kg/day, for 4 months Receives: Drug: phenobarbital |
| Placebo | Placebo comparator | Placebo in a volume equivalent to active drug for 4 months Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Bayley Scales of Infant Development (BSID) Score - Cognitive
The Bayley Scales of Infant Development (BSID) measure the mental and motor development and test the behavior of infants from one to 42 months of age. The test is intended to measure a child's level of development in three domains: cognitive, motor, and behavioral. The primary outcome is the Bayley assessment of development at 2 years of age. This is a standardized developmental exam that is normalized to the age of the child in months. The mean adjusted score is 100 with a standard deviation of 15 (higher being better) - very similar to the more familiar IQ score.
Measured: 18-22 months
Secondary outcomes (2)
Mean Bayley Scales of Infant Development (BSID) Score - Motor
This part of the BSID assesses the degree of body control, large muscle coordination, finer manipulatory skills of the hands and fingers, dynamic movement, postural imitation, and the ability to recognize objects by sense of touch.
Measured: 18-22 months
Number of Participants With One or More Seizures
Any clinical or electrographic seizures occurring between study entry and all follow-up examinations and contacts.
Measured: 18-22 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2010 (estimated)
- Study startSep 2010
- Primary completionNov 2014
- Study completionNov 2014
Why it stopped: Inadequate rate of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neonatal SeizuresStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ronnie Guillet, University of Rochester
- Investigators
- Ronnie Guillet, MD, PhD, Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01089504
- Sponsor's protocol ID
- 28907
- Acronym
- PROPHENO
- Status last verified
- Jan 2016
- First submitted
- 17 Mar 2010
- Last updated
- 3 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prophylactic Phenobarbital After Resolution of Neonatal Seizures
- ClinicalTrials.gov ID
- NCT01089504
- Acronym / sponsor ID
- PROPHENO / 28907
- Conditions
- Neonatal Seizures
- Keywords
- phenobarbital, neonate, antiepileptic drugs, neurodevelopmental outcome, seizure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inadequate rate of enrollment
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Study start
- Sep 2010
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 18 Mar 2010 (estimated)
- Results
- Posted 3 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The treatment of infants with medications after their seizures have stopped is very variable. No one knows if continuing treatment with phenobarbital for up to several months is helpful or harmful. This clinical trial is designed to help answer that question and provide data that will help determine standard of care for these children.
Detailed description
The treatment of infants with antiepileptic medications after the resolution of neonatal seizures is highly variable and controversial. Infants are commonly treated with phenobarbital after their seizures have resolved to prevent recurrence. Data to support this practice are lacking but animal models suggest that the neonatal brain is vulnerable to repeated seizures. Yet exposure of the developing brain to phenobarbital for prolonged periods may have deleterious consequences. We are proposing a multi-center, randomized, clinical trial (RCT) to determine if continued treatment with phenobarbital reduces seizure recurrence without adversely affecting neurodevelopmental outcome or if infants' outcomes are improved if no prophylactic medication is given. We will identify infants with seizures beginning in the first week that resolve within 7 days and randomize them to receive phenobarbital or placebo daily for four months. Via visits and frequent telephone contacts over the first six months, we will determine the rate of seizure recurrence. The primary outcome, neurodevelopmental status, will be assessed at 18-22 months using the Bayley Scales of Infant Development. Additional subgroup analyses are planned to determine the contribution of seizure etiology to outcome and predictive value of initial EEG classification. The trial will be conducted at 18 - 20 sites, chosen for their experience and proven track record for enrollment and retention in this specific population. The trial will be coordinated by the Clinical Trials Coordination Center at the University of Rochester and overseen by a Steering Committee composed of experienced trialists representing neonatology and pediatric neurology, biostatistics, and clinical trial administration.
Extrapolation from the results of an RCT of phenobarbital prophylaxis after febrile seizures in children suggests that phenobarbital may adversely affect brain development and may be ineffective in preventing seizures. Based on this previous RCT that resulted in near universal change in practice (the elimination of prolonged use of phenobarbital after simple febrile seizures), we anticipate that the data we generate may have a similar impact on standard of care for infants with neonatal seizures.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phenobarbital | Active comparator | Drug: phenobarbitalPhenobarbital, 4-5 mg/kg/day, for 4 months |
| Placebo | Placebo comparator | Drug: placeboPlacebo in a volume equivalent to active drug for 4 months |
Who may qualify
- Ages
- 2 days to 2 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Birth at > 34 weeks' gestation
- Neonatal seizures (clinical, electrographic or both), with onset in the first 120 hours after birth and resolution within 7 days of onset
- Parental informed consent
Key exclusion criteria (5 listed)
- Birth at < 34 weeks' gestation
- If the attending neonatologist attributes the seizures solely to a transient abnormality, easily correctable and unlikely to recur (eg, transient electrolyte abnormalities). If the attending neonatologist cannot be contacted, the site PI will be asked to review the available information and judge whether the infant is eligible.
- If the infant has been diagnosed with or there is a strong suspicion of an inborn error of metabolism, significant brain malformation, microcephaly (< 3 %ile), or a chromosomal abnormality which, in the absence of seizures, is known to be independently associated with an increased likelihood of cognitive impairment
- If the infant has been diagnosed with an intrauterine viral infection
- If the infant is not expected to survive to discharge
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 |
|---|---|---|
| phenobarbitalPhenobarbital, 4-5 mg/kg/d, by mouth, for 4 months | Drug | Phenobarbital |
| placeboMatched placebo, same volume as active drug, by mouth daily for 4 months | Drug | Placebo |
Primary outcome
Mean Bayley Scales of Infant Development (BSID) Score - Cognitive
Time frame: 18-22 months
The Bayley Scales of Infant Development (BSID) measure the mental and motor development and test the behavior of infants from one to 42 months of age. The test is intended to measure a child's level of development in three domains: cognitive, motor, and behavioral. The primary outcome is the Bayley assessment of development at 2 years of age. This is a standardized developmental exam that is normalized to the age of the child in months. The mean adjusted score is 100 with a standard deviation of 15 (higher being better) - very similar to the more familiar IQ score.
2 secondary outcomes
Mean Bayley Scales of Infant Development (BSID) Score - Motor
Time frame: 18-22 months
Number of Participants With One or More Seizures
Time frame: 18-22 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Ronnie Guillet, MD, PhD principal investigator
University of Rochester
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing phenobarbital in people with Neonatal Seizures, run by University of Rochester at 18 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 3 inclusion and 5 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: stopped early, as of the sponsor's last update on 3 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mean Bayley Scales of Infant Development (BSID) Score - Cognitive (time frame: 18-22 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Feb 2016; AzTrials last refreshed its copy on 30 Oct 2026.