Study to Evaluate Phenobarbital Sodium Injection for the Treatment of Neonatal Seizures

August 26, 2019 updated by: PharPoint Research, Inc.

A Randomized, Double-blind, Parallel Group, Phase 3 Study to Evaluate the Efficacy of Phenobarbital Sodium Injection for the Treatment of Neonatal Seizures

This is a randomized, double-blind, parallel-group, Phase 3 study to evaluate the efficacy of the administration of phenobarbital Sodium Injection, United States Pharmacopeia, (USP), in participants who have suffered from a clinical 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 phenobarbital is effective at preventing subsequent seizures by demonstrating greater efficacy at the higher (40 mg/kg) dose compared to the lower dose (20 mg/kg). It is important to note that, although phenobarbital is not approved for the treatment of neonatal seizures, it is commonly used for this indication and is considered the first-line therapy in the US and by the World Health Organization. The minimum recommended dose of phenobarbital used to treat neonatal seizures is 20 mg/kg. Therefore, the lower dose of phenobarbital used in this study is considered an "effective" dose for the treatment of neonatal seizures. The design of this study allows for assessment of the minimum recommended dose with the maximum recommended dose to show the increased efficacy of the high dose in various measures of reduction in seizures.

Study Overview

Status

Withdrawn

Conditions

Detailed Description

This is a randomized, double-blind, parallel-group, Phase 3 study to evaluate the efficacy of the administration of Phenobarbital Sodium Injection, USP in participants who have suffered from a clinical 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 phenobarbital is effective at preventing subsequent seizures by demonstrating greater efficacy at the higher (40 mg/kg) dose compared to the lower dose (20 mg/kg). It is important to note that, although phenobarbital is not approved for the treatment of neonatal seizures, it is commonly used for this indication and is considered the first-line therapy in the United States, (US), and by the World Health Organization. The minimum recommended dose of phenobarbital used to treat neonatal seizures is 20 mg/kg. Therefore, the lower dose of phenobarbital used in this study is considered an "effective" dose for the treatment of neonatal seizures. The design of this study allows for assessment of the minimum recommended dose with the maximum recommended dose to show the increased efficacy of the high dose in various measures of reduction in seizures.

Study participants undergoing electrographic or electroclinical seizures lasting 10 seconds or longer will be randomized in a 1:1 fashion between the 2 treatment arms. Participants will receive either a 20-mg/kg or 40-mg/kg loading dose of Phenobarbital Sodium Injection, USP upon confirmation that the seizure was not due to metabolic imbalances. Randomization of participants with hypoxic-ischemic encephalopathy, (HIE), will be stratified between the dosing groups. Participants will further be stratified by treatment group for pharmacokinetics, (PK), analysis timepoints due to the limitations on the number of pharmacokinetics, (PK), samples that can be taken from each patient. After cessation of seizures the participants will remain in the hospital for 24 hours for continuous monitoring by electroencephalogram, (EEG).

According to recommended dosing of phenobarbital, participants in the 20-mg/kg treatment arm in whom seizure activity does not resolve after the first dose (20 mg/kg) will be given phenobarbital in 10-mg/kg increments (each hour) until the seizure activity resolves, up to a maximum total dose of 40 mg/kg. If the seizure activity is still not resolved, participants will be given a second-line anticonvulsant. The second-line therapy given will be determined by the attending physician and recorded in the study documentation. Participants in the 40-mg/kg treatment arm in whom seizure activity does not resolve after the initial loading dose of phenobarbital will be given a second-line anticonvulsant. The second therapy given will be determined by the attending physician and recorded in the study documentation.

Study Type

Interventional

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 day to 4 weeks (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Parental informed consent
  2. Infants born at ≥ 35 + 0/7 weeks gestational age AND age 0-28 days after birth
  3. Has evidence of an electrographic seizure lasting at least 10 seconds
  4. Undergoing continuous electroencephalogram, (EEG), monitoring, including infants with hypoxic-ischemic encephalopathy concurrently treated with hypothermic cooling

Exclusion Criteria:

  1. If the seizures are solely due to a transient abnormality, easily correctable, and unlikely to recur (for example, transient electrolyte abnormalities)
  2. If the infant has been diagnosed with or there is a strong suspicion of an inborn error of metabolism, significant brain malformation, or microcephaly (< 3rd percentile)
  3. If the infant has been diagnosed with an intrauterine viral infection
  4. If the infant is not expected to survive to discharge

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Phenobarbital Sodium Injection 20 mg
Once participants are deemed to be eligible for participation in the study and randomized to the lower dose they will be given a loading dose of phenobarbital 20 mg/kg administered intravenously over the course of 30 minutes.
Phenobarbitone Inj, Phenobarbitone SOD, Phenobarbitone Sodium
Other Names:
  • Phenobarbital Sodium Injection 20 mg
  • Phenobarbital Sodium Injection 40 mg
Active Comparator: Phenobarbital Sodium Injection 40 mg
Once participants are deemed to be eligible for participation in the study and randomized to the higher dose they will be given a loading dose of phenobarbital 20 mg/kg administered intravenously over the course of 30 minutes. ministered intravenously over the course of 30 minutes.
Phenobarbitone Inj, Phenobarbitone SOD, Phenobarbitone Sodium
Other Names:
  • Phenobarbital Sodium Injection 20 mg
  • Phenobarbital Sodium Injection 40 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
A change in the number of seizures in neonatal infants after administration of phenobarbital sodium injection
Time Frame: The 24 hour period after the initial loading dose of pheonobarbital sodium injection is given.
Once a neonate has been identified as having a seizure by electroencephalogram he/she will be randomized to one of two doses of phenobarbital sodium injection, (20 mg/kg or 40 mg/kg). The number of neonates in each group will be observed for the end of any further seizures, also verified by electroencephalogram. In addition to observing when all seizure activity ended after the initial loading dose, the number of infants requiring a second dose of phenobarbital or second-line anti-convulsant therapy to treat unresolved or subsequent seizures will be observed in each randomization group, (phenobarbital sodium injection 20mg/kg or 40mg/kg) following the initial loading dose.
The 24 hour period after the initial loading dose of pheonobarbital sodium injection is given.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

November 1, 2019

Primary Completion (Anticipated)

May 1, 2021

Study Completion (Anticipated)

August 1, 2021

Study Registration Dates

First Submitted

July 17, 2018

First Submitted That Met QC Criteria

July 25, 2018

First Posted (Actual)

July 26, 2018

Study Record Updates

Last Update Posted (Actual)

August 28, 2019

Last Update Submitted That Met QC Criteria

August 26, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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