Efficacy and Safety of Intravenous Phenobarbital in Neonatal Seizures

Phase 3

Terminated

Brief Summary: This is a randomized, double-blind, parallel-group, Phase 3 study to evaluate the efficacy of the administration of phenobarbital sodium injection in neonates who have suffered from electrographic or electroclinical seizure. As neonatal seizures can have long-term adverse effects, including death, placebo-controlled studies are not appropriate for this population. This study is designed to show intravenous phenobarbital is effective at preventing subsequent seizures by demonstrating greater efficacy at a higher dose compared to a lower dose.

Recruitment & Eligibility

Inclusion Criteria

Male or female neonates with a gestational age of ≥ 34 - ≤44 weeks admitted into the NICU with a high probability of developing seizures (e.g., HIE, stroke, intracerebral hemorrhage, central nervous system infection)
Parental informed consent (in-person or remote consent)
Undergoing continuous video electroencephalogram (cvEEG) monitoring
Has evidence of electrographic seizure burden of at least 30 seconds/h

Exclusion Criteria

Received anticonvulsant treatment, including phenobarbital, prior to randomization (with exception of lorazepam administered for sedation > 24 hours before enrollment)
Strong suspicion or confirmed diagnosis of brain malformation, inborn error of metabolism genetic syndrome, or major congenial malformation prior to randomization
Seizures responding to correction of hypoglycemia, hypocalcemia or any other metabolic disorder
Death appears to be imminent as assessed by the NICU attending physician
Is currently enrolled in another study assessing the same and/or similar primary/secondary endpoints with/without drug treatment.

Arm && Interventions

Group	Intervention	Description
Phenobarbital Sodium Injection 20mg	Phenobarbital Sodium Injection	Following confirmation of seizure criteria and randomization, subjects will receive Phenobarbital 20 mg/kg (first/initial dose) followed by 20 mg/kg (if required).
Phenobarbital Sodium Injection 40mg	Phenobarbital Sodium Injection	Following confirmation of seizure criteria and randomization, subjects will receive Phenobarbital 40 mg/kg (first/initial dose) followed by 10 mg/kg (if required).

Primary Outcome Measures

Name	Time	Method
Neonates Who do Not Require Additional Seizure Treatment After the First Dose of Phenobarbital.	24 hours	Percent of neonates who do not require additional seizure treatment after the first dose of phenobarbital during the first 24 hours after treatment.

Secondary Outcome Measures

Name	Time	Method
Neonates Who do Not Require Additional Seizure Treatment After the Second Dose of Phenobarbital.	24 hours	Percent of neonates who do not require additional seizure treatment after the second dose of phenobarbital within the first 24 hours of treatment.
Neonates Who do Not Require Additional Seizure Treatment After the First Dose of Phenobarbital.	2 hours	Percent of neonates who do not require additional seizure treatment after 2 hours of the first dose of phenobarbital.
Seizure Burden Over 48 Hours Following Initial Administration of the Phenobarbital Injection.	48 hours	Number of subject required monitoring of seizure burden over 48 hours following initial administration of the phenobarbital injection.

Locations (8): UPMC Children's Hospital of Pittsburgh
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Pittsburgh, Pennsylvania, United States
Marshall Health
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Huntington, West Virginia, United States
South Miami Hospital
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Miami, Florida, United States
Arkansas Cildren's Hospital
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Little Rock, Arkansas, United States
Children's National Hospital
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Washington, District of Columbia, United States
Matthew Butoryak
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Pittsburgh, Pennsylvania, United States
Jamie Flores-Torres
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Tampa, Florida, United States
Jordan University of Science and Technology (King Abdullah University Hospital, KAUH)
🇯🇴
Irbid', Jordan