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Prophylactic Phenobarbital After Neonatal Seizures (PROPHENO)

This study has been terminated.
(Inadequate rate of enrollment)
Sponsor:
Information provided by (Responsible Party):
Ronnie Guillet, University of Rochester
ClinicalTrials.gov Identifier:
NCT01089504
First received: March 17, 2010
Last updated: June 8, 2012
Last verified: June 2012

March 17, 2010
June 8, 2012
September 2010
November 2014   (final data collection date for primary outcome measure)
Bayley Scales of Infant Development [ Time Frame: 18-22 months ] [ Designated as safety issue: No ]
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. We propose to use mental development as the primary outcome for this trial.
Same as current
Complete list of historical versions of study NCT01089504 on ClinicalTrials.gov Archive Site
  • Bayley Scales of Infant Development - Motor [ Time Frame: 18-22 months ] [ Designated as safety issue: No ]
    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.
  • Seizure recurrence [ Time Frame: 18-22 months ] [ Designated as safety issue: No ]
    Any clinical or electrographic seizures occurring between study entry and all follow-up examinations and contacts.
Same as current
Not Provided
Not Provided
 
Prophylactic Phenobarbital After Neonatal Seizures
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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Neonatal Seizures
  • Drug: phenobarbital
    Phenobarbital, 4-5 mg/kg/d, by mouth, for 4 months
  • Drug: placebo
    Matched placebo, same volume as active drug, by mouth daily for 4 months
  • Active Comparator: Phenobarbital
    Phenobarbital, 4-5 mg/kg/day, for 4 months
    Intervention: Drug: phenobarbital
  • Placebo Comparator: Placebo
    Placebo in a volume equivalent to active drug for 4 months
    Intervention: Drug: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
13
November 2014
November 2014   (final data collection date for primary outcome measure)

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
Both
up to 2 Weeks
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01089504
28907
Yes
Ronnie Guillet, University of Rochester
University of Rochester
Not Provided
Principal Investigator: Ronnie Guillet, MD, PhD University of Rochester
University of Rochester
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP