Efficacy and Safety of Intravenous Phenobarbital in Neonatal Seizures

Sponsor

NEMA Research, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04320940

Collaborator

(none)

490

Enrollment

Locations

Arms

21.6

Anticipated Duration (Months)

81.7

Patients Per Site

3.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy, Benign Neonatal	Drug: Phenobarbital Sodium Injection	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

490 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 12, 2021

Anticipated Primary Completion Date :

Dec 28, 2022

Anticipated Study Completion Date :

Dec 28, 2022

Arms and Interventions

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

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

Other Names:

Phenobarbital

Outcome Measures

Primary Outcome Measures

Neonates who do not require additional seizure treatment after the first dose of phenobarbital. [24 hours]
Percent of neonates who do not require additional seizure treatment after the first dose of phenobarbital during the first 24 hours after treatment.

Secondary Outcome Measures

Neonates who do not require additional seizure treatment after the first dose of phenobarbital. [2 hours]
Percent of neonates who do not require additional seizure treatment after 2 hours of the first dose of phenobarbital.
Neonates who do not require additional seizure treatment after the second dose of phenobarbital. [24 hours]
Percent of neonates who do not require additional seizure treatment after the second dose of phenobarbital within the first 24 hours of treatment.
Seizure burden [48 hours]
Seizure burden over 48 hours following initial administration of the phenobarbital injection.

Eligibility Criteria

Criteria

Ages Eligible for Study:

34 Weeks to 44 Weeks

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's National Hospital	Washington	District of Columbia	United States	20010
2	University of South Florida	Tampa	Florida	United States	33606
3	Maine Medical Center	Portland	Maine	United States	04102
4	UPMC Magee Womens	Pittsburgh	Pennsylvania	United States	15213
5	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
6	Marshall Health	Huntington	West Virginia	United States	25701