Efficacy and Safety of Intravenous Phenobarbital in Neonatal Seizures

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

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.

Study Overview

• Status: Terminated
• Conditions: Epilepsy, Benign Neonatal
• Intervention / Treatment: Drug: Phenobarbital Sodium Injection

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 3

Contacts and Locations

Study Locations

• Jordan
  • Irbid', Jordan, 22110
    • Jordan University of Science and Technology (King Abdullah University Hospital, KAUH)
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Cildren's Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Hospital
  • Florida
    • Miami, Florida, United States, 33143
      • South Miami Hospital
    • Tampa, Florida, United States, 33606
      • Jamie Flores-Torres
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
    • Pittsburgh, Pennsylvania, United States, 15213
      • Matthew Butoryak
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Marshall Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 10 months (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Phenobarbital Sodium Injection 20mg; 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; 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.; Other Names: Phenobarbital
Active Comparator: Phenobarbital Sodium Injection 40mg; 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; 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.; Other Names: Phenobarbital

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: NEMA Research, Inc.
• Investigators: Principal Investigator: Joseph Pergolizzi Jr., MD, MD, NEMA Research, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2021
• Primary Completion (Actual): February 1, 2023
• Study Completion (Actual): February 1, 2023

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: March 23, 2020
• First Posted (Actual): March 25, 2020

Study Record Updates

• Last Update Posted (Actual): October 26, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Neonatal Seizures; Anticonvulsants; Phenobarbital
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Infant, Newborn, Diseases; Epilepsy; Seizures; Epilepsy, Benign Neonatal; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Hypnotics and Sedatives; GABA Modulators; GABA Agents; Anticonvulsants; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Phenobarbital
• Other Study ID Numbers: MI-5780

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No