Prophylactic Phenobarbital After Neonatal Seizures
- Registration Number
- NCT01089504
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 13
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo placebo Placebo in a volume equivalent to active drug for 4 months Phenobarbital phenobarbital Phenobarbital, 4-5 mg/kg/day, for 4 months
- Primary Outcome Measures
Name Time Method Mean Bayley Scales of Infant Development (BSID) Score - Cognitive 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
Name Time Method Mean Bayley Scales of Infant Development (BSID) Score - Motor 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.
Number of Participants With One or More Seizures 18-22 months Any clinical or electrographic seizures occurring between study entry and all follow-up examinations and contacts.
Trial Locations
- Locations (18)
Women & Infants Hospital of Rhode Island
🇺🇸Providence, Rhode Island, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
University of Arkansas
🇺🇸Little Rock, Arkansas, United States
Univeristy of Iowa
🇺🇸Iowa City, Iowa, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
University of Rochester
🇺🇸Rochester, New York, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Women & Children's Hospital of Buffalo
🇺🇸Buffalo, New York, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Forsyth Medical Center
🇺🇸Winston Salem, North Carolina, United States
Wake Forest University
🇺🇸Winston Salem, North Carolina, United States
Magee Womens Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States