Neonatal SeizurePhase 3NCT03602118
Study to Evaluate Phenobarbital Sodium Injection for the Treatment of Neonatal Seizures
A Phase 3 study testing Phenobarbital Sodium Injection in people with Neonatal Seizure, run by PharPoint Research, Inc..
Trial 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. Read more about this study
- Who is it for?
- Ages 1 day to 28 days
- Conditions the study is for
- Neonatal Seizure
- What is being tested?
- Phenobarbital Sodium Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Nov 2019to 1 Aug 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 28 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
About this study
Official title: 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.
Read the 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.
- Conditions
- Neonatal Seizure
- Being tested
- Phenobarbital Sodium Injection
- Keywords
- clinical seizures,
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phenobarbital Sodium InjectionDrug
Also called Phenobarbital Sodium Injection 20 mg, Phenobarbital Sodium Injection 40 mg
Phenobarbitone Inj, Phenobarbitone SOD, Phenobarbitone Sodium
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Phenobarbital Sodium Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: The 24 hour period after the initial loading dose of pheonobarbital sodium injection is given.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2018
- Study startNov 2019 (estimated)
- Primary completion1 May 2021 (estimated)
- Study completion1 Aug 2021 (estimated)
Why it stopped: Sponsor withdrawing the subject IND
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neonatal SeizureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a 1:1 randomized, double-blind, parallel-group, Phase 3 study.
- Masking
- Double blind
- Who is masked
- Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- PharPoint Research, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03602118
- Sponsor's protocol ID
- 1021.121.039.00
- Status last verified
- Aug 2019
- First submitted
- 17 Jul 2018
- Last updated
- 28 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Parallel Group, Phase 3 Study to Evaluate the Efficacy of Phenobarbital Sodium Injection for the Treatment of Neonatal Seizures
- ClinicalTrials.gov ID
- NCT03602118
- Acronym / sponsor ID
- 1021.121.039.00
- Conditions
- Neonatal Seizure
- Keywords
- clinical seizures,
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor withdrawing the subject IND
- Enrolment
- 0 participants (actual)
- Lead sponsor
- PharPoint Research, Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2019 (estimated)
- Primary completion
- 1 May 2021 (estimated)
- Study completion
- 1 Aug 2021 (estimated)
- First posted
- 26 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, investigator)
- Number of arms
- 2
- Model description
- This is a 1:1 randomized, double-blind, parallel-group, Phase 3 study.
| Arm | Type | Receives |
|---|---|---|
| Phenobarbital Sodium Injection 20 mg | Active comparator | Drug: Phenobarbital Sodium InjectionOnce 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. |
| Phenobarbital Sodium Injection 40 mg | Active comparator | Drug: Phenobarbital Sodium InjectionOnce 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. |
Who may qualify
- Ages
- 1 day to 28 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Phenobarbital Sodium InjectionAlso: Phenobarbital Sodium Injection 20 mg, Phenobarbital Sodium Injection 40 mgPhenobarbitone Inj, Phenobarbitone SOD, Phenobarbitone Sodium | Drug | Phenobarbital Sodium Injection 20 mg, Phenobarbital Sodium Injection 40 mg |
Primary outcome
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.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Phenobarbital Sodium Injection in people with Neonatal Seizure, run by PharPoint Research, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2019.