Clinical trial NCT01089504: Prophylactic Phenobarbital After Neonatal Seizures
Official title: Prophylactic Phenobarbital After Resolution of Neonatal Seizures
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Neonatal Seizures
Keywords: phenobarbital
neonate
antiepileptic drugs
neurodevelopmental outcome
seizure
Lead sponsor: University of Rochester
Sponsor class: OTHER
First posted: 2010-03-18
Enrollment: 13
Sex: ALL
Minimum age (years): 2
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Bayley Scales of Infant Development (BSID) Score - Cognitive
timeFrame: 18-22 months
Secondary outcomes:
measure: Mean Bayley Scales of Infant Development (BSID) Score - Motor
timeFrame: 18-22 months
measure: Number of Participants With One or More Seizures
timeFrame: 18-22 months
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas
state: Arkansas
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Iowa City
country: United States
facility: Univeristy of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Buffalo
country: United States
facility: Women & Children's Hospital of Buffalo
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Winston Salem
country: United States
facility: Forsyth Medical Center
state: North Carolina
city: Winston Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Pittsburgh
country: United States
facility: Magee Womens Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: University of Rochester
name: Ronnie Guillet, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: