Epilepsy, Benign Neonatal
Conditions
Keywords
Neonatal Seizures, Phenobarbital, Anticonvulsants
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.
Interventions
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.
Sponsors
NEMA Research, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
34 Weeks to 44 Weeks
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 Over 48 Hours Following Initial Administration of the Phenobarbital Injection. | 48 hours | Number of subject required monitoring of seizure burden over 48 hours following initial administration of the phenobarbital injection. |
Countries
Jordan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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).
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. | 3 |
| 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).
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. | 1 |
| Total | 4 |
Baseline characteristics
| Characteristic | Phenobarbital Sodium Injection 20mg | Phenobarbital Sodium Injection 40mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 0 Participants | 3 Participants |
| Region of Enrollment United States | 3 participants | 1 participants | 4 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 1 |
| other Total, other adverse events | 0 / 3 | 0 / 1 |
| serious Total, serious adverse events | 1 / 3 | 0 / 1 |
Outcome results
Primary
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.
Time frame: 24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phenobarbital Sodium Injection 20mg | Neonates Who do Not Require Additional Seizure Treatment After the First Dose of Phenobarbital. | 2 Participants |
| Phenobarbital Sodium Injection 40mg | Neonates Who do Not Require Additional Seizure Treatment After the First Dose of Phenobarbital. | 1 Participants |
Secondary
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.
Time frame: 2 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phenobarbital Sodium Injection 20mg | Neonates Who do Not Require Additional Seizure Treatment After the First Dose of Phenobarbital. | 2 Participants |
| Phenobarbital Sodium Injection 40mg | Neonates Who do Not Require Additional Seizure Treatment After the First Dose of Phenobarbital. | 1 Participants |
Secondary
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.
Time frame: 24 hours
Population: Three subjects (two in the low-dose and one in the high-dose groups) received a first dose and no subsequent doses of the medication. One subject in the low-dose group received an initial dose (20 mg/kg) at 14:10 on July 15 and a second dose (20 mg/kg) at 17:25 on the same day.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phenobarbital Sodium Injection 20mg | Neonates Who do Not Require Additional Seizure Treatment After the Second Dose of Phenobarbital. | 1 Participants |
| Phenobarbital Sodium Injection 40mg | Neonates Who do Not Require Additional Seizure Treatment After the Second Dose of Phenobarbital. | 0 Participants |
Secondary
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.
Time frame: 48 hours
Population: One subject in the low-dose group received an initial dose (20 mg/kg) at 14:10 on July 15 and a second dose (20 mg/kg) at 17:25 on the same day. Maintenance doses of 5 mg/kg were administered to this subject once daily on July 16, 17, and 18. Only this subject required monitoring of seizure burden over 48 hours following initial administration of the phenobarbital injection
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phenobarbital Sodium Injection 20mg | Seizure Burden Over 48 Hours Following Initial Administration of the Phenobarbital Injection. | 1 Participants |
| Phenobarbital Sodium Injection 40mg | Seizure Burden Over 48 Hours Following Initial Administration of the Phenobarbital Injection. | 0 Participants |