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Prophylactic Phenobarbital After Neonatal Seizures (PROPHENO)

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: NCT01089504
Recruitment Status : Terminated (Inadequate rate of enrollment)
First Posted : March 18, 2010
Results First Posted : February 3, 2016
Last Update Posted : February 3, 2016
Information provided by (Responsible Party):
Ronnie Guillet, University of Rochester

Brief 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. This clinical trial is designed to help answer that question and provide data that will help determine standard of care for these children.

Condition or disease Intervention/treatment Phase
Neonatal Seizures Drug: phenobarbital Drug: placebo Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prophylactic Phenobarbital After Resolution of Neonatal Seizures
Study Start Date : September 2010
Actual Primary Completion Date : November 2014
Actual Study Completion Date : November 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Seizures

Arm Intervention/treatment
Active Comparator: Phenobarbital
Phenobarbital, 4-5 mg/kg/day, for 4 months
Drug: phenobarbital
Phenobarbital, 4-5 mg/kg/d, by mouth, for 4 months

Placebo Comparator: Placebo
Placebo in a volume equivalent to active drug for 4 months
Drug: placebo
Matched placebo, same volume as active drug, by mouth daily for 4 months

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Mean Bayley Scales of Infant Development (BSID) Score - Motor [ Time Frame: 18-22 months ]
    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.

  2. Number of Participants With One or More Seizures [ Time Frame: 18-22 months ]
    Any clinical or electrographic seizures occurring between study entry and all follow-up examinations and contacts.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 2 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

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): NCT01089504

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Sponsors and Collaborators
University of Rochester
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Principal Investigator: Ronnie Guillet, MD, PhD University of Rochester
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Responsible Party: Ronnie Guillet, Professor, University of Rochester Identifier: NCT01089504    
Other Study ID Numbers: 28907
First Posted: March 18, 2010    Key Record Dates
Results First Posted: February 3, 2016
Last Update Posted: February 3, 2016
Last Verified: January 2016
Keywords provided by Ronnie Guillet, University of Rochester:
antiepileptic drugs
neurodevelopmental outcome
Additional relevant MeSH terms:
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Neurologic Manifestations
Nervous System 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