Prophylactic Phenobarbital After Neonatal Seizures

Neonatal Seizures Clinical Trial

— PROPHENO  

Official title:

Prophylactic Phenobarbital After Resolution of Neonatal Seizures

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01089504
• Other study ID #: 28907
• Status: Terminated
• Phase: Phase 4
• First received: March 17, 2010
• Last updated: January 4, 2016
• Start date: September 2010
• Est. completion date: November 2014

Study information

• Verified date: January 2016
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

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

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 information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 2 Weeks

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neonatal Seizures
• Seizures

Intervention

Drug:
• phenobarbital
Phenobarbital, 4-5 mg/kg/d, by mouth, for 4 months
• placebo
Matched placebo, same volume as active drug, by mouth daily for 4 months

Locations

Country	Name	City	State
United States	Akron Children's Hospital	Akron	Ohio
United States	University of Michigan	Ann Arbor	Michigan
United States	Johns Hopkins University	Baltimore	Maryland
United States	Tufts Medical Center	Boston	Massachusetts
United States	Women & Children's Hospital of Buffalo	Buffalo	New York
United States	University of Virginia	Charlottesville	Virginia
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Univeristy of Iowa	Iowa City	Iowa
United States	University of Arkansas	Little Rock	Arkansas
United States	Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Women & Infants Hospital of Rhode Island	Providence	Rhode Island
United States	University of Rochester	Rochester	New York
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	University of Utah	Salt Lake City	Utah
United States	University of California San Francisco	San Francisco	California
United States	Forsyth Medical Center	Winston Salem	North Carolina
United States	Wake Forest University	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
University of Rochester

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	18-22 months	No
Secondary	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.	18-22 months	No
Secondary	Number of Participants With One or More Seizures	Any clinical or electrographic seizures occurring between study entry and all follow-up examinations and contacts.	18-22 months	No