Efficacy and Safety of Intravenous Phenobarbital in Neonatal Seizures

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Double-Blind, Controlled Study to Assess the Efficacy and Safety of Intravenous Phenobarbital in Neonatal Seizures

Conditions
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Epilepsy, Benign Neonatal

Intervention / Treatment
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* Drug: Phenobarbital Sodium Injection


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 34 Weeks
Maximum Age: 44 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Phenobarbital Sodium Injection 20mg<br>Following confirmation of seizure criteria and randomization, subjects will receive Phenobarbital 20 mg/kg (first/initial dose) followed by 20 mg/kg (if required). | Drug: Phenobarbital Sodium Injection<br>* The initial dose will be administered intravenously over a 30-minute period. The time period between the first and second dose of phenobarbital cannot occur within 30 minutes of the end of the first dose.<br>* Other names: Phenobarbital;|
| Active Comparator: Phenobarbital Sodium Injection 40mg<br>Following confirmation of seizure criteria and randomization, subjects will receive Phenobarbital 40 mg/kg (first/initial dose) followed by 10 mg/kg (if required). | Drug: Phenobarbital Sodium Injection<br>* The initial dose will be administered intravenously over a 30-minute period. The time period between the first and second dose of phenobarbital cannot occur within 30 minutes of the end of the first dose.<br>* Other names: Phenobarbital;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neonates Who do Not Require Additional Seizure Treatment After the First Dose of Phenobarbital. | Percent of neonates who do not require additional seizure treatment after the first dose of phenobarbital during the first 24 hours after treatment. | 24 hours | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neonatal Seizures, Phenobarbital, Anticonvulsants