Efficacy and Safety of Intravenous Phenobarbital in Neonatal Seizures

NCT04320940 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: MI-5780
• Study Type: interventional
• Target: 4
• Locations: 2 countries
• Sites: 8

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.

Conditions

Epilepsy, Benign Neonatal

Keywords

Neonatal Seizures; Phenobarbital; Anticonvulsants

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Neonates Who do Not Require Additional Seizure Treatment After the First Dose of Phenobarbital.

  2 hours

• Neonates Who do Not Require Additional Seizure Treatment After the Second Dose of Phenobarbital.

  24 hours

• Seizure Burden Over 48 Hours Following Initial Administration of the Phenobarbital Injection.

  48 hours

Study Arms (2)

Phenobarbital Sodium Injection 20mg

ACTIVE COMPARATOR

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

Phenobarbital Sodium Injection 40mg

ACTIVE COMPARATOR

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

Interventions

Phenobarbital Sodium Injection DRUG

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.

Also known as: Phenobarbital

Phenobarbital Sodium Injection 20mg; Phenobarbital Sodium Injection 40mg

Eligibility Criteria

• Age: 34 Weeks - 44 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• NEMA Research, Inc.: lead

Study Sites (8)

Arkansas Cildren's Hospital

Little Rock, Arkansas, 72202, United States

Location

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

South Miami Hospital

Miami, Florida, 33143, United States

Location

Jamie Flores-Torres

Tampa, Florida, 33606, United States

Location

Matthew Butoryak

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Marshall Health

Huntington, West Virginia, 25701, United States

Location

Jordan University of Science and Technology (King Abdullah University Hospital, KAUH)

Irbid, 22110, Jordan

Location

MeSH Terms

Conditions

Epilepsy, Benign Neonatal

Interventions

Phenobarbital

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Amy Schutte
• Organization: Hikma Pharmaceuticals

aschutte@Hikma.com

440-201-5010

Study Officials

• Joseph Pergolizzi Jr., MD, MD

  NEMA Research, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2020
• First Posted: March 25, 2020
• Study Start: March 12, 2021
• Primary Completion: February 1, 2023
• Study Completion: February 1, 2023
• Last Updated: October 26, 2023
• Results First Posted: October 26, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); JO (1)