Neonatal SeizuresPhase 1/2NEOLEV2NCT01720667
Efficacy of Intravenous Levetiracetam in Neonatal Seizures
A Phase 1/2 study testing Intravenous levetiracetam and Intravenous phenobarbital in people with Neonatal Seizures, run by Richard H. Haas at 1 site in United States.
Trial summary
A new anticonvulsant, levetiracetam will be studied to treat seizures in newborn infants. Current treatments for the brain damaging complication of neonatal seizures are unsatisfactory. Monitoring for seizure detection will be tested at five (5) US sites and one (1) international site using the internet. Read more about this study
- Who is it for?
- Ages 15 minutes to 14 days
- Conditions the study is for
- Neonatal Seizures
- What is being tested?
- Intravenous levetiracetam and Intravenous phenobarbital
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 280 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to 31 Jul 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 15 minutes to 14 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Newborns admitted to any of the study sites with electrographic seizures seizures.
- Term infants gestational age >36 weeks less than 2 weeks of age.
- Greater than 2200 grams.
- Infants for whom parental consent to participate in the study is obtained.
Who cannot join
- Infants who are already receiving anticonvulsants
- If serum creatinine is greater than 1.6mM
- If seizures are due to correctable metabolic abnormalities (i.e. hypoglycaemia, hypocalcemia, hyponatremia)
- Subjects in whom death seems imminent, as assessed by the neonatologist.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego Medical Center / Neonatal Intensive Care Unit (NICU)
San Diego, California, 92103
About this study
Official title: Efficacy of Intravenous Levetiracetam in Neonatal Seizures: A Phase 2 Randomized Blinded Controlled Study of the Efficacy of Intravenous Levetiracetam (LEV) as First Line Treatment for Neonatal Seizures
A new anticonvulsant, levetiracetam will be studied to treat seizures in newborn infants. Current treatments for the brain damaging complication of neonatal seizures are unsatisfactory.
Monitoring for seizure detection will be tested at five (5) US sites and one (1) international site using the internet.
Read the detailed description
This project aims to improve the treatment of neonatal seizures. Current treatments are poorly effective and have significant side effects.
Levetiracetam (LEV) has great potential as a treatment for neonatal seizures but is not approved for use in children less than 2 years of age.
This study aims to obtain essential data regarding the efficacy and safety of LEV in this vulnerable and under researched population and simultaneously to develop EEG monitoring systems that facilitate seizure detection and research.
Specific aims are:
- To determine the efficacy of intravenous LEV in terminating neonatal seizures when given as first line therapy.
- To obtain dose escalation data by studying the additional efficacy of a further dose in non responders.
- To obtain additional pharmacokinetic data to confirm findings from our previous pharmacokinetic study.
- To obtain further safety data of LEV in neonates.
- To prove the feasibility of centralized remote monitoring of continuous EEG monitoring in the Neonatal Intensive Care Unit (NICU) via the internet and test a promising automated neonatal seizure detection algorithm.
The study design is a phase 2b randomized blinded controlled study.
- Conditions
- Neonatal Seizures
- Being tested
- Intravenous levetiracetam, Intravenous phenobarbital
- Keywords
- Seizures, Neonates, Anticonvulsants, Treatment, Levetiracetam, Phenobarbital
- Medical subject headings
- Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous levetiracetamDrug
Also called Keppra
Intravenous load of levetiracetam (40 to 60 mg/kg) following identification of EEG confirmed neonatal seizure.
Intravenous phenobarbitalDrug
Also called phenobarbitone
Intravenous load of phenobarbital (20 to 40 mg/kg) following EEG confirmation of seizure activity load.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous levetiracetam | Experimental | Intravenous levetiracetam 40 to 60 mg/kg loading dose. 10 mg/kg 8 hourly maintenance Receives: Drug: Intravenous levetiracetam |
| Intravenous phenobarbital | Active comparator | Intravenous phenobarbital 20 to 40 mg/kg load. 1.5 mg/kg 8 hourly maintenance Receives: Drug: Intravenous phenobarbital |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neonates With Seizure Cessation When Given Levetiracetam (40-60 mg/kg) as First Line Therapy Compared to Phenobarbital (20-40mg/kg)
A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.
Seizure cessation from 15 minutes after completion of infusion for 24 hours as assessed by continuous EEG reviewed by neurophysiologists.
Measured: 24 hours
Secondary outcomes (4)
Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital at 48 Hours After Treatment
A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.
Measured: 48 hours
Number of Neonates With Seizure Termination at 1 Hour After Treatment
A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.
Measured: 1 hour
LEV Dose Escalation Component
Number of babies with seizure control at levetiracetam (60 mg/Kg load) who had not responded to 40 mg/kg load and number of babies with seizure control at 40 mg/kg who had not responded to 20 mg/kg.
Measured: 24 hours
Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital Within the Hypoxic Ischemic Encephalopathy (HIE) Population and Treated With Hypothermia
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2012 (estimated)
- Study startMar 2013
- Primary completion31 Oct 2017
- Study completion31 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Neonatal SeizuresStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 280 participants (actual)
Sponsor and investigators
- Lead sponsor
- Richard H. Haas
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, San Diego, Rady Children's Hospital, San Diego, Auckland City Hospital, Sharp Mary Birch Hospital for Women & Newborns, UCSF Benioff Children's Hospital Oakland, Food and Drug Administration (FDA)
- Responsible party
- Sponsor-investigator, Richard H. Haas, University of California, San Diego
- Investigators
- Richard H Haas, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01720667
- Sponsor's protocol ID
- NoGA - R01 FD004147-01A1 Haas
- Other IDs
- 1R01FD004147-01A1
- Acronym
- NEOLEV2
- Status last verified
- Aug 2019
- First submitted
- 22 Oct 2012
- Last updated
- 21 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Sharpe CM, Capparelli EV, Mower A, Farrell MJ, Soldin SJ, Haas RH. A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life. Pediatr Res. 2012 Jul;72(1):43-9. doi: 10.1038/pr.2012.51. Epub 2012 Apr 11.
PubMed 22495532Sharpe C, Davis SL, Reiner GE, Lee LI, Gold JJ, Nespeca M, Wang SG, Joe P, Kuperman R, Gardner M, Honold J, Lane B, Knodel E, Rowe D, Battin MR, Bridge R, Goodmar J, Castro B, Rasmussen M, Arnell K, Harbert M, Haas R. Assessing the Feasibility of Providing a Real-Time Response to Seizures Detected With Continuous Long-Term Neonatal Electroencephalography Monitoring. J Clin Neurophysiol. 2019 Jan;36(1):9-13. doi: 10.1097/WNP.0000000000000525.
PubMed 30289769Sharpe C, Yang DZ, Haas RH, Reiner GE, Lee L, Capparelli EV; NEOLEV2 Investigators. Pharmacokinetic and pharmacodynamic data from the NEOLEV1 and NEOLEV2 studies. Arch Dis Child. 2024 Sep 25;109(10):854-860. doi: 10.1136/archdischild-2022-324952.
PubMed 38902005
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Intravenous Levetiracetam in Neonatal Seizures: A Phase 2 Randomized Blinded Controlled Study of the Efficacy of Intravenous Levetiracetam (LEV) as First Line Treatment for Neonatal Seizures
- ClinicalTrials.gov ID
- NCT01720667
- Acronym / sponsor ID
- NEOLEV2 / NoGA - R01 FD004147-01A1 Haas
- Conditions
- Neonatal Seizures
- Keywords
- Seizures, Neonates, Anticonvulsants, Treatment, Levetiracetam, Phenobarbital
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 280 participants (actual)
- Lead sponsor
- Richard H. HaasUniversity, hospital or other
- Collaborators
- University of California, San Diego, Rady Children's Hospital, San Diego, Auckland City Hospital, Sharp Mary Birch Hospital for Women & Newborns, UCSF Benioff Children's Hospital Oakland, Food and Drug Administration (FDA)
- Study start
- Mar 2013 (actual)
- Primary completion
- 31 Oct 2017 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 2 Nov 2012 (estimated)
- Results
- Posted 21 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A new anticonvulsant, levetiracetam will be studied to treat seizures in newborn infants. Current treatments for the brain damaging complication of neonatal seizures are unsatisfactory.
Monitoring for seizure detection will be tested at five (5) US sites and one (1) international site using the internet.
Detailed description
This project aims to improve the treatment of neonatal seizures. Current treatments are poorly effective and have significant side effects.
Levetiracetam (LEV) has great potential as a treatment for neonatal seizures but is not approved for use in children less than 2 years of age.
This study aims to obtain essential data regarding the efficacy and safety of LEV in this vulnerable and under researched population and simultaneously to develop EEG monitoring systems that facilitate seizure detection and research.
Specific aims are:
- To determine the efficacy of intravenous LEV in terminating neonatal seizures when given as first line therapy.
- To obtain dose escalation data by studying the additional efficacy of a further dose in non responders.
- To obtain additional pharmacokinetic data to confirm findings from our previous pharmacokinetic study.
- To obtain further safety data of LEV in neonates.
- To prove the feasibility of centralized remote monitoring of continuous EEG monitoring in the Neonatal Intensive Care Unit (NICU) via the internet and test a promising automated neonatal seizure detection algorithm.
The study design is a phase 2b randomized blinded controlled study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous levetiracetam | Experimental | Drug: Intravenous levetiracetamIntravenous levetiracetam 40 to 60 mg/kg loading dose. 10 mg/kg 8 hourly maintenance |
| Intravenous phenobarbital | Active comparator | Drug: Intravenous phenobarbitalIntravenous phenobarbital 20 to 40 mg/kg load. 1.5 mg/kg 8 hourly maintenance |
Who may qualify
- Ages
- 15 minutes to 14 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Newborns admitted to any of the study sites with electrographic seizures seizures.
- Term infants gestational age >36 weeks less than 2 weeks of age.
- Greater than 2200 grams.
- Infants for whom parental consent to participate in the study is obtained.
Key exclusion criteria (4 listed)
- Infants who are already receiving anticonvulsants
- If serum creatinine is greater than 1.6mM
- If seizures are due to correctable metabolic abnormalities (i.e. hypoglycaemia, hypocalcemia, hyponatremia)
- Subjects in whom death seems imminent, as assessed by the neonatologist.
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 |
|---|---|---|
| Intravenous levetiracetamAlso: KeppraIntravenous load of levetiracetam (40 to 60 mg/kg) following identification of EEG confirmed neonatal seizure. | Drug | Intravenous levetiracetam |
| Intravenous phenobarbitalAlso: phenobarbitoneIntravenous load of phenobarbital (20 to 40 mg/kg) following EEG confirmation of seizure activity load. | Drug | Intravenous phenobarbital |
Primary outcome
Neonates With Seizure Cessation When Given Levetiracetam (40-60 mg/kg) as First Line Therapy Compared to Phenobarbital (20-40mg/kg)
Time frame: 24 hours
A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures. Seizure cessation from 15 minutes after completion of infusion for 24 hours as assessed by continuous EEG reviewed by neurophysiologists.
4 secondary outcomes
Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital at 48 Hours After Treatment
Time frame: 48 hours
Number of Neonates With Seizure Termination at 1 Hour After Treatment
Time frame: 1 hour
LEV Dose Escalation Component
Time frame: 24 hours
Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital Within the Hypoxic Ischemic Encephalopathy (HIE) Population and Treated With Hypothermia
Time frame: 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22495532Sharpe CM, Capparelli EV, Mower A, Farrell MJ, Soldin SJ, Haas RH. A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life. Pediatr Res. 2012 Jul;72(1):43-9. doi: 10.1038/pr.2012.51. Epub 2012 Apr 11.
- Results publication: PubMed 30289769Sharpe C, Davis SL, Reiner GE, Lee LI, Gold JJ, Nespeca M, Wang SG, Joe P, Kuperman R, Gardner M, Honold J, Lane B, Knodel E, Rowe D, Battin MR, Bridge R, Goodmar J, Castro B, Rasmussen M, Arnell K, Harbert M, Haas R. Assessing the Feasibility of Providing a Real-Time Response to Seizures Detected With Continuous Long-Term Neonatal Electroencephalography Monitoring. J Clin Neurophysiol. 2019 Jan;36(1):9-13. doi: 10.1097/WNP.0000000000000525.
- Derived from this study: PubMed 38902005Sharpe C, Yang DZ, Haas RH, Reiner GE, Lee L, Capparelli EV; NEOLEV2 Investigators. Pharmacokinetic and pharmacodynamic data from the NEOLEV1 and NEOLEV2 studies. Arch Dis Child. 2024 Sep 25;109(10):854-860. doi: 10.1136/archdischild-2022-324952.
Related trials for Neonatal Seizures
RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
Not yet recruitingPhase 4
Study of Electrocardiogram (ECG) Safety of Sezaby in Neonatal Seizures
Neonatal Seizure
RecruitingObservational study
Genetic Markers of Cardiovascular Disease in Epilepsy
Epilepsy, Seizures
Recruiting
FITting Non-invasive Tests in Lynch Syndrome Surveillance
Colorectal Cancer
RecruitingPhase 2
A Dose Escalation Study of Levetiracetam in the Treatment of Neonatal Seizures
Neonatal Seizure, Neonatal Encephalopathy
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.
Richard H Haas, MD principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Intravenous levetiracetam and Intravenous phenobarbital in people with Neonatal Seizures, run by Richard H. Haas at 1 site in United States.
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: finished, as of the sponsor's last update on 21 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Neonates With Seizure Cessation When Given Levetiracetam (40-60 mg/kg) as First Line Therapy Compared to Phenobarbital (20-40mg/kg) (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01720667, which also lists 3 linked publications.
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 21 Aug 2019.