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

NCT03602118 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: 1021.121.039.00
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Neonatal Seizure

Keywords

clinical seizures,

Outcome Measures

Primary Outcomes (1)

• A change in the number of seizures in neonatal infants after administration of phenobarbital sodium injection

  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.

Study Arms (2)

Phenobarbital Sodium Injection 20 mg

ACTIVE COMPARATOR

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.

Drug: Phenobarbital Sodium Injection

Phenobarbital Sodium Injection 40 mg

ACTIVE COMPARATOR

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.

Drug: Phenobarbital Sodium Injection

Interventions

Phenobarbital Sodium Injection DRUG

Phenobarbitone Inj, Phenobarbitone SOD, Phenobarbitone Sodium

Also known as: Phenobarbital Sodium Injection 20 mg, Phenobarbital Sodium Injection 40 mg

Phenobarbital Sodium Injection 20 mg; Phenobarbital Sodium Injection 40 mg

Eligibility Criteria

• Age: 1 Day - 28 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• If the seizures are solely due to a transient abnormality, easily correctable, and unlikely to recur (for example, transient electrolyte abnormalities)
• 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)
• If the infant has been diagnosed with an intrauterine viral infection
• If the infant is not expected to survive to discharge

Sponsors & Collaborators

• PharPoint Research, Inc.: lead

MeSH Terms

Interventions

Phenobarbital

Intervention Hierarchy (Ancestors)

Barbiturates; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, INVESTIGATOR
• Masking Details: All efforts will be made to blind the investigator and other key personnel of which dosage the participant was randomized to. Study drug will be dispensed by the pharmacy via a syringe to the investigator or their designee. The study medication label should only contain the protocol number, subject number and any other pertinent information. If after 1 hour following the completion of the study drug infusion, the seizure is not controlled with the initial loading dose, the patient will be considered a treatment failure in the primary efficacy analysis of this protocol/study. At this point, the blinding for the treating provider/investigator will be lifted.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a 1:1 randomized, double-blind, parallel-group, Phase 3 study.

Study Record Dates

• First Submitted: July 17, 2018
• First Posted: July 26, 2018
• Study Start: November 1, 2019
• Primary Completion: May 1, 2021
• Study Completion: August 1, 2021
• Last Updated: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share