Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 1R01FD004147-01A1 | U.S. FDA Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of California, San Diego | OTHER |
| Rady Children's Hospital, San Diego | OTHER |
| Auckland City Hospital | OTHER_GOV |
| Sharp Mary Birch Hospital for Women & Newborns |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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:
The study design is a phase 2b randomized blinded controlled study.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intravenous levetiracetam | Experimental | Intravenous levetiracetam 40 to 60 mg/kg loading dose. 10 mg/kg 8 hourly maintenance |
|
| Intravenous phenobarbital | Active Comparator | Intravenous phenobarbital 20 to 40 mg/kg load. 1.5 mg/kg 8 hourly maintenance |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intravenous levetiracetam | Drug | Intravenous load of levetiracetam (40 to 60 mg/kg) following identification of EEG confirmed neonatal seizure. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 48 hours |
| Number of Neonates With Seizure Termination at 1 Hour After Treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic Data | To obtain additional pharmacokinetic data "Area under the plasma concentration versus time curve (AUC) and Peak Plasma Concentration (Cmax)" of intravenous levetiracetam to confirm findings from our previous pharmacokinetic study. | 48 hours |
| Feasibility of Continuous Internet EEG Monitoring |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Richard H Haas, MD | University of California, San Diego | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Diego Medical Center / Neonatal Intensive Care Unit (NICU) | San Diego | California | 92103 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22495532 | Background | 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. | |
| 30289769 | Result | Sharpe 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. |
Not provided
Not provided
280 were enrolled to EEG monitoring and of these 106 were randomized to treatment as neonatal seizures were thought to have occurred. 174 excluded as they did not have electrographic seizures; from 6 participants only verbal not written consent obtained.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Intravenous Levetiracetam | Intravenous levetiracetam 40 - 60 mg/kg loading dose. If electrographic seizures persisted or recurred 15 minutes following completion of the infusion, subjects received a further 20 mg/kg LEV infusion over 15 minutes. If electrographic seizures persisted or recurred 15 minutes following completion of the second infusion, the subject was then treated with PHB 20 mg/kg. Another dose of 20 mg/kg PHB given if seizures persist. Unresponsive subjects exit the study. All subjects received maintenance LEV 10 mg/kg/dose given IV q8 hours continued for five days. |
| FG001 | Intravenous Phenobarbital | Intravenous phenobarbital 20 mg/kg loading dose. If electrographic seizures persisted or recurred 15 minutes following completion of the infusion, subjects received a further 20 mg/kg PHB infusion over 15 minutes. If electrographic seizures persisted or recurred 15 minutes following completion of the second infusion, the subject was then treated with LEV 40 mg/kg first. Another dose of 20 mg/kg PHB given if seizures persist. Unresponsive subjects exit the study. All subjects received maintenance 1.5 mg/kg PHB mg/kg/dose given IV q8 hours continued for five days. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Intravenous Levetiracetam | Intravenous levetiracetam 40 to 60 mg/kg loading dose. 10 mg/kg 8 hourly maintenance Intravenous levetiracetam: Intravenous load of levetiracetam (40 to 60 mg/kg) following identification of EEG confirmed neonatal seizure. |
| BG001 | Intravenous Phenobarbital |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Treated participants with available primary outcome measure- EEG to 24 hours confirming seizure cessation. | Posted | Count of Participants | Participants | 24 hours |
|
Up to 5 days after treatment
Data not collected separately for each intervention
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intravenous Phenobarbital | Intravenous phenobarbital 20 mg/kg loading dose. If electrographic seizures persisted or recurred 15 minutes following completion of the infusion, subjects received a further 20 mg/kg PHB infusion over 15 minutes. If electrographic seizures persisted or recurred 15 minutes following completion of the second infusion, the subject was then treated with LEV 40 mg/kg first. Another dose of 20 mg/kg PHB given if seizures persist. Unresponsive subjects exit the study. All subjects received maintenance 1.5 mg/kg PHB mg/kg/dose given IV q8 hours continued for five days. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Vascular disorders | Systematic Assessment | Grade 4 hypotension thought probably or possibly due to study medications |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Vascular disorders | Systematic Assessment | Specific finding of hypotension on a day on which an adverse event was indicated. |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Richard Haas | University of California San Diego, School of Medicine | (858) 822-6700 | rhaas@ucsd.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 14, 2018 | Jun 14, 2019 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Apr 13, 2018 | Jun 14, 2019 | Prot_001.pdf |
Not provided
| ID | Term |
|---|---|
| D012640 | Seizures |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077287 | Levetiracetam |
| D010634 | Phenobarbital |
| ID | Term |
|---|---|
| D000081 | Acetamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000085 | Acetates |
| D000144 |
Not provided
Not provided
| OTHER |
| UCSF Benioff Children's Hospital Oakland | OTHER |
| Food and Drug Administration (FDA) | FED |
Not provided
Not provided
Not provided
Not provided
|
| Intravenous phenobarbital | Drug | Intravenous load of phenobarbital (20 to 40 mg/kg) following EEG confirmation of seizure activity load. |
|
|
A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures. |
| 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. | 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 | 24 hours |
Feasibility of centralized remote access to continuous video EEG monitoring in the NICU via the internet |
| Subject study duration |
| Evaluation of the Accuracy of Neonatal Seizure Detection Algorithm | A novel neonatal seizure detection algorithm will be compared to the gold standard of two encephalographers reading 48 hours of neonatal video EEG in the measurement of seizure burden. | 48 Hours |
| Gather Safety Information on IV Levetiracetam | Safety information to be collected includes daily recording of any adverse events during the 5 day treatment protocol. Complete Blood Count and Comprehensive Chemistry panels after 48 hours of treatment collected. | 5 days |
| 38902005 | Derived | Sharpe 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. |
Intravenous phenobarbital 20 to 40 mg/kg load. 1.5 mg/kg 8 hourly maintenance Intravenous phenobarbital: Intravenous load of phenobarbital (20 to 40 mg/kg) following EEG confirmation of seizure activity load. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Intravenous phenobarbital 20 - 40 mg/kg loading dose & 1.5 mg/kg 8 hourly maintenance. |
|
|
|
| Secondary | 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. | Participants with evaluable data with 48 hours of seizure monitoring | Posted | Count of Participants | Participants | 48 hours |
|
|
|
|
| Secondary | 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. | Includes 1 participant in each arm who did not have data available for the primary end point at 24 hours | Posted | Count of Participants | Participants | 1 hour |
|
|
|
| Secondary | 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. | Babies who received any treatment of either phenobarbital or levetiracetam within the modified intent to treat | Posted | Count of Participants | Participants | 24 hours |
|
|
|
| Secondary | 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 | HIE participants with hypothermia treatment | Posted | Count of Participants | Participants | 24 hours |
|
|
|
| Other Pre-specified | Pharmacokinetic Data | To obtain additional pharmacokinetic data "Area under the plasma concentration versus time curve (AUC) and Peak Plasma Concentration (Cmax)" of intravenous levetiracetam to confirm findings from our previous pharmacokinetic study. | Not Posted | 48 hours | Participants |
| Other Pre-specified | Feasibility of Continuous Internet EEG Monitoring | Feasibility of centralized remote access to continuous video EEG monitoring in the NICU via the internet | Not Posted | Subject study duration | Participants |
| Other Pre-specified | Evaluation of the Accuracy of Neonatal Seizure Detection Algorithm | A novel neonatal seizure detection algorithm will be compared to the gold standard of two encephalographers reading 48 hours of neonatal video EEG in the measurement of seizure burden. | Not Posted | 48 Hours | Participants |
| Other Pre-specified | Gather Safety Information on IV Levetiracetam | Safety information to be collected includes daily recording of any adverse events during the 5 day treatment protocol. Complete Blood Count and Comprehensive Chemistry panels after 48 hours of treatment collected. | Not Posted | Sep 2019 | 5 days | Participants |
| Post-Hoc | Imputation Sensitivity Analysis | Analysis of missing data impact on the outcome measures | Not Posted | 48 hours | Participants |
| 1 |
| 42 |
| 5 |
| 42 |
| 13 |
| 42 |
| EG001 | Intravenous Levetiracetam | Intravenous levetiracetam 40 - 60 mg/kg loading dose. If electrographic seizures persisted or recurred 15 minutes following completion of the infusion, subjects received a further 20 mg/kg LEV infusion over 15 minutes. If electrographic seizures persisted or recurred 15 minutes following completion of the second infusion, the subject was then treated with PHB 20 mg/kg. Another dose of 20 mg/kg PHB given if seizures persist. Unresponsive subjects exit the study. All subjects received maintenance LEV 10 mg/kg/dose given IV q8 hours continued for five days. | 2 | 64 | 1 | 64 | 12 | 64 |
|
| Respiratory Abnormality | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Grade 4 respiratory distress thought probably or possibly due to study medication |
|
| Heart Rate Abnormality | Cardiac disorders | Systematic Assessment |
|
| Sedation | Nervous system disorders | Systematic Assessment |
|
| Poor Feeding | Gastrointestinal disorders | Systematic Assessment |
|
| Infection | Infections and infestations | Systematic Assessment |
|
| New Medications | General disorders | Systematic Assessment |
|
|
| Heart Rate Abnormailty | Cardiac disorders | Systematic Assessment | Specific finding of heart rate abnormality on a day on which an adverse event was reported |
|
| Respiratory Abnormality | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Specific finding of respiratory abnormality documented on a day on which an adverse event was documented |
|
| Sedation | Nervous system disorders | Systematic Assessment | Specific finding of sedation on a day on which an adverse event was documented |
|
| Poor Feeding | Gastrointestinal disorders | Systematic Assessment | Specific finding of poor feeding on a day on which adverse event was documented |
|
| Infection | Infections and infestations | Systematic Assessment | Specific finding of infection on a day on which adverse event was documented |
|
| New Medical Problem | General disorders | Systematic Assessment | New Medical Problem reported on a day where an adverse event is documented |
|
| New Medications | General disorders | Systematic Assessment |
|
| Vasopressor Requirement | Cardiac disorders | Systematic Assessment | Hypotension requiring vasopressor support on at least one day |
|
Not provided
Not provided
| Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D011760 | Pyrrolidinones |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001463 | Barbiturates |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |