Neonatal SeizuresPhase 2LEVNEONAT-1NCT02229123
Levetiracetam Treatment of Neonatal Seizures: Safety and Efficacy Phase II Study
A Phase 2 study testing Intravenous Levetiracetam in people with Neonatal Seizures, run by University Hospital, Tours at 8 sites in France.
Trial summary
LEVNEONAT is a multicentre French clinical trials with the aim to develop new treatment strategies for the treatment of neonatal seizures using Levetiracetam. The purpose of this study is to determine the correct dosing, safety and efficacy for intravenous levetiracetam as first line treatment in term newborn babies… Read more about this study
- Who is it for?
- Ages 36 to 43 weeks
- Conditions the study is for
- Neonatal Seizures
- What is being tested?
- Intravenous Levetiracetam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 8 sitesFrance
- Study dates
- 27 Feb 2018to 23 Feb 2022
- Phase
- Phase 2
- 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 36 to 43 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- A seizure lasting more than 3 minutes or more than 2 seizures lasting more than 20 seconds on a 1 hour-period on standard EEG recording 4 hours before the levetiracetam loading dose
- Availability of 8 electrode EEG recording
- Written informed consent of both parents or the authorized guardians
- Subscription to social security health insurance are required
Who cannot join
- Suspected or confirmed brain malformation, inborn error of metabolism, genetic syndrome or major congenital malformation
- Congenital (in utero) infection (TORCH)
- Babies who have received phenobarbital or any other anticonvulsive medication other than a bolus of midazolam for intubation
- Anuria/renal failure defined as serum creatinine > 150 micromol/L
- Seizures secondary to treatable metabolic etiology as hypoglycemia and hypocalcemia
- Corrected QT interval (QTc) greater than 450 milliseconds on the electrocardiogram (ECG) prior to inclusion in the presence or absence of a condition that promotes QT prolongation (hypokalemia, maternal treatment during childbirth or treatment of the child with drugs known to prolong QT),
- Participation to an interventional research study
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
France8 sites
Service de réanimation néonatale
Angers, 49000
Service de réanimation néonatale
Lille, 59037
Service de réanimation et service néonatale
Orléans, 45100
Service de réanimation néonatale et pédiatrique
Paris, 75012
Service de réanimation néonatale
Reims, 51092
Néonatologie
Rennes, 35000
Service de Pédiatrie néonatale et réanimation
Rouen, 76031
Service de Néonatologie
Tours, 37 000
About this study
Official title: Levetiracetam Efficacy and Safety as First-line Treatment of Neonatal Seizures Occuring in Hypoxic-ischemic Encephalopathy Context
LEVNEONAT is a multicentre French clinical trials with the aim to develop new treatment strategies for the treatment of neonatal seizures using Levetiracetam. The purpose of this study is to determine the correct dosing, safety and efficacy for intravenous levetiracetam as first line treatment in term newborn babies with seizures in hypoxic-ischemic encephalopathy context. This new anticonvulsivant drug is a promising treatment for seizures in newborns.
Read the detailed description
Article Focus
- The principal aim of LEVNEONAT-1 is to determine the levetiracetam optimal dose defined as the highest efficient dose under toxicity restrictions for treating neonatal seizures.
- LEVNEONAT-1 is an open-label, sequential dose-finding study with 3 increasing dose levels of levetiracetam.
Strenghts and limitation of study
- For the first time, levetiracetam will be used as the first-line treatment of neonatal seizures and not as an add-on therapy.
- Statistical model is designed for a rare clinical situation with a sequential adaptive method updating in real time the dose allocation for next patient by using all available data from previous participants.
- The targeted population, i.e. the newborn less than 3 days of life, is particularly sensitive and the written consent of both parents is required before the levetiracetam administration.
- Conditions
- Neonatal Seizures
- Being tested
- Intravenous Levetiracetam
- Keywords
- seizures, neonates, anticonvulsant treatment, levetiracetam, hypoxic-ischemic encephalopathy, electroencephalography
- Medical subject headings
- Seizures, Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous LevetiracetamDrug
Open-study. If seizure lasting more than 3 minutes on EEG recording or brief repeated seizures (more or equal to 2 seizures lasting more than 20 seconds on a 1 hour-interval), the loading-dose of LEV allocated to patient is infused followed by the 8 maintenance dose.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous levetiracetam | Experimental | 1 loading dose of 30, 40 or 50 mg/kg administered intra-venously. Maintenance treatment: one intra-venous injection /8h, 8 doses in total for a 3-day treatment. Maintenance dose corresponds to the loading dose quarter i.e. 7.5, 10 or 12.5 mg/kg. Receives: Drug: Intravenous Levetiracetam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Levetiracetam Efficacy on EEG recording
Efficacy has been defined as an 80% reduction of seizure burden on EEG recording.
Measured: the period just before the LEV loading dose (from 20 min to 3 hours) and the 3 hour time-interval from 1 hour 15 min (T11/4) to 4 hours 15 min (T41/4) after the starting of loading dose infusion (T0)
Levetiracetam Short-Term Toxicity
Short-term toxicity focuses on 4 adverse events potentially attributable to LEV occurring in the 6 days following the loading dose: i) Severe apnoea leading to mechanical ventilation during the 4-hour period following the LEV infusion; ii) Anaphylactic shock occurring during the 30 minutes following the LEV infusion; iii) Toxic epidermic necrosis; iv) Stevens-Jonhson Syndrome. Short-term toxicity has been designed to trigger quickly a decreasing dose allocation to the next potential participant through a e-CRF alert.
Measured: 6 days from the loading dose
Levetiracetam Long-Term Toxicity
Long-term toxicity includes all the adverse events observed and declared to the pharmacovigilance unit up to the hospital discharge or the 30th day of life at the latest.
Measured: 30 days from the loading dose
Secondary outcomes (7)
Levetiracetam Elimination Clearance
The mean values of the elimination clearance and their respective interindividual variability will be estimated.
Measured: at 30 min, 4 hours and 7 hours after the end of loading dose infusion, respectively and at 1 to 3 hours and 12 hours to 18 hours after the last levetiracetam maintenance dose, respectively.
Levetiracetam Distribution Volume
The mean values of distribution volumes and their respective interindividual variability will be estimated.
Measured: at 30 min, 4 hours and 7 hours after the end of loading dose infusion, respectively and at 1 to 3 hours and 12 hours to 18 hours after the last levetiracetam maintenance dose, respectively.
Plasmatic Levetiracetam Maximal Concentration
Plasmatic Peak Value of Levetiracetam Loading dose will be assessed.
Measured: 30 min, 4 hours and 7 hours after the end of Levetiracetam loading dose infusion
Levetiracetam Loading Dose Area under Curve
ndividual PK parameters will be estimated and used to calculated the AUC corresponding to the loading dose, after the first maintenance dose.
Measured: 30 min, 4 hours and 7 hours after the end of Levetiracetam loading dose infusion
Levetiracetam Entire Treatment Area Under Curve
Individual PK parameters will be estimated and used to calculated the cumulative AUC of the entire treatment.
Measured: at 30 min, 4 hours and 7 hours after the end of loading dose infusion, respectively and at 1 to 3 hours and 12 hours to 18 hours after the last Levetiracetam maintenance dose, respectively.
Seizure recurrence from the Efficacy criteria completion to day 6
Clinical or electric seizures recurrence after the efficacy criteria assessment and up to the complete levetiracetam elimination (estimated 5 half-life) will be reported by investigator.
Measured: from 4h15 after the loading dose to 6 days
Levetiracetam Efficacy according to the seizure burden intensity prior to loading dose
A new analysis will be performed retrospectively by adjusting the efficacy criteria to the seizure burden on the pre-treatment EEG. Two subgroups will be considered according to the seizure burden (SB) intensity on the pre-treatment EEG, i.e equal or above to 50% of the EEG recording duration (high SB group) and strictly under 50% of it (low SB group), respectively. LEV efficacy will be considered positive when a SB reduction of 50% will be observed on the post-treatment EEG recording in the high SB group whereas the reduction of 80% will be still valid for the low SB group.
Measured: after the complete recruting period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2014 (estimated)
- Study start27 Feb 2018
- Primary completion23 Feb 2022
- Study completion23 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neonatal SeizuresStudies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- LEVNEONAT-1 is an open and sequential dose-finding study with 1 loading dose of 30, 40 and 50 mg/kg and 8 quarter-loading maintenance doses for a 3-day treatment. The optimal dose will be the one estimated to be associated with a toxicity not exceeding 10% and an efficacy higher than 60%. Efficacy has been defined by a seizure burden reduction of 80% after the loading dose. A 2-patient cohort will be necessary at each dose level to consider an upper dose level assignment with a dynamic consideration of each participant data. The maximal sample size expected is 30 participants patients.
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Collaborators
- Assistance Publique - Hôpitaux de Paris, Rennes University Hospital, Amiens University Hospital
- Responsible party
- Sponsor
- Investigators
- Geraldine Favrais, Dr, Study chair, University Hospital of ToursGeraldine FAVRAIS, Dr, Principal investigator, University hospital of Tours
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02229123
- Sponsor's protocol ID
- 2014-000791-26
- Other IDs
- 2014
- Acronym
- LEVNEONAT-1
- Status last verified
- Dec 2025
- First submitted
- 27 Aug 2014
- Last updated
- 30 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Favrais G, Ursino M, Mouchel C, Boivin E, Jullien V, Zohar S, Saliba E. Levetiracetam optimal dose-finding as first-line treatment for neonatal seizures occurring in the context of hypoxic-ischaemic encephalopathy (LEVNEONAT-1): study protocol of a phase II trial. BMJ Open. 2019 Jan 24;9(1):e022739. doi: 10.1136/bmjopen-2018-022739.
PubMed 30679288
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Levetiracetam Efficacy and Safety as First-line Treatment of Neonatal Seizures Occuring in Hypoxic-ischemic Encephalopathy Context
- ClinicalTrials.gov ID
- NCT02229123
- Acronym / sponsor ID
- LEVNEONAT-1 / 2014-000791-26
- Conditions
- Neonatal Seizures
- Keywords
- seizures, neonates, anticonvulsant treatment, levetiracetam, hypoxic-ischemic encephalopathy, electroencephalography
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Collaborators
- Assistance Publique - Hôpitaux de Paris, Rennes University Hospital, Amiens University Hospital
- Study start
- 27 Feb 2018 (actual)
- Primary completion
- 23 Feb 2022 (actual)
- Study completion
- 23 Feb 2022 (actual)
- First posted
- 29 Aug 2014 (estimated)
- 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.
LEVNEONAT is a multicentre French clinical trials with the aim to develop new treatment strategies for the treatment of neonatal seizures using Levetiracetam. The purpose of this study is to determine the correct dosing, safety and efficacy for intravenous levetiracetam as first line treatment in term newborn babies with seizures in hypoxic-ischemic encephalopathy context. This new anticonvulsivant drug is a promising treatment for seizures in newborns.
Detailed description
Article Focus
- The principal aim of LEVNEONAT-1 is to determine the levetiracetam optimal dose defined as the highest efficient dose under toxicity restrictions for treating neonatal seizures.
- LEVNEONAT-1 is an open-label, sequential dose-finding study with 3 increasing dose levels of levetiracetam.
Strenghts and limitation of study
- For the first time, levetiracetam will be used as the first-line treatment of neonatal seizures and not as an add-on therapy.
- Statistical model is designed for a rare clinical situation with a sequential adaptive method updating in real time the dose allocation for next patient by using all available data from previous participants.
- The targeted population, i.e. the newborn less than 3 days of life, is particularly sensitive and the written consent of both parents is required before the levetiracetam administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- LEVNEONAT-1 is an open and sequential dose-finding study with 1 loading dose of 30, 40 and 50 mg/kg and 8 quarter-loading maintenance doses for a 3-day treatment. The optimal dose will be the one estimated to be associated with a toxicity not exceeding 10% and an efficacy higher than 60%. Efficacy has been defined by a seizure burden reduction of 80% after the loading dose. A 2-patient cohort will be necessary at each dose level to consider an upper dose level assignment with a dynamic consideration of each participant data. The maximal sample size expected is 30 participants patients.
| Arm | Type | Receives |
|---|---|---|
| Intravenous levetiracetam | Experimental | Drug: Intravenous Levetiracetam1 loading dose of 30, 40 or 50 mg/kg administered intra-venously. Maintenance treatment: one intra-venous injection /8h, 8 doses in total for a 3-day treatment. Maintenance dose corresponds to the loading dose quarter i.e. 7.5, 10 or 12.5 mg/kg. |
Who may qualify
- Ages
- 36 to 43 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- A seizure lasting more than 3 minutes or more than 2 seizures lasting more than 20 seconds on a 1 hour-period on standard EEG recording 4 hours before the levetiracetam loading dose
- Availability of 8 electrode EEG recording
- Written informed consent of both parents or the authorized guardians
- Subscription to social security health insurance are required
Key exclusion criteria (7 listed)
- Suspected or confirmed brain malformation, inborn error of metabolism, genetic syndrome or major congenital malformation
- Congenital (in utero) infection (TORCH)
- Babies who have received phenobarbital or any other anticonvulsive medication other than a bolus of midazolam for intubation
- Anuria/renal failure defined as serum creatinine > 150 micromol/L
- Seizures secondary to treatable metabolic etiology as hypoglycemia and hypocalcemia
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 LevetiracetamOpen-study. If seizure lasting more than 3 minutes on EEG recording or brief repeated seizures (more or equal to 2 seizures lasting more than 20 seconds on a 1 hour-interval), the loading-dose of LEV allocated to patient is infused followed by the 8 maintenance dose. | Drug | Intravenous levetiracetam |
Primary outcome
Levetiracetam Efficacy on EEG recording
Time frame: the period just before the LEV loading dose (from 20 min to 3 hours) and the 3 hour time-interval from 1 hour 15 min (T11/4) to 4 hours 15 min (T41/4) after the starting of loading dose infusion (T0)
Efficacy has been defined as an 80% reduction of seizure burden on EEG recording.
Levetiracetam Short-Term Toxicity
Time frame: 6 days from the loading dose
Short-term toxicity focuses on 4 adverse events potentially attributable to LEV occurring in the 6 days following the loading dose: i) Severe apnoea leading to mechanical ventilation during the 4-hour period following the LEV infusion; ii) Anaphylactic shock occurring during the 30 minutes following the LEV infusion; iii) Toxic epidermic necrosis; iv) Stevens-Jonhson Syndrome. Short-term toxicity has been designed to trigger quickly a decreasing dose allocation to the next potential participant through a e-CRF alert.
Levetiracetam Long-Term Toxicity
Time frame: 30 days from the loading dose
Long-term toxicity includes all the adverse events observed and declared to the pharmacovigilance unit up to the hospital discharge or the 30th day of life at the latest.
7 secondary outcomes
Levetiracetam Elimination Clearance
Time frame: at 30 min, 4 hours and 7 hours after the end of loading dose infusion, respectively and at 1 to 3 hours and 12 hours to 18 hours after the last levetiracetam maintenance dose, respectively.
Levetiracetam Distribution Volume
Time frame: at 30 min, 4 hours and 7 hours after the end of loading dose infusion, respectively and at 1 to 3 hours and 12 hours to 18 hours after the last levetiracetam maintenance dose, respectively.
Plasmatic Levetiracetam Maximal Concentration
Time frame: 30 min, 4 hours and 7 hours after the end of Levetiracetam loading dose infusion
Levetiracetam Loading Dose Area under Curve
Time frame: 30 min, 4 hours and 7 hours after the end of Levetiracetam loading dose infusion
Levetiracetam Entire Treatment Area Under Curve
Time frame: at 30 min, 4 hours and 7 hours after the end of loading dose infusion, respectively and at 1 to 3 hours and 12 hours to 18 hours after the last Levetiracetam maintenance dose, respectively.
Seizure recurrence from the Efficacy criteria completion to day 6
Time frame: from 4h15 after the loading dose to 6 days
Levetiracetam Efficacy according to the seizure burden intensity prior to loading dose
Time frame: after the complete recruting period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2025.
- Results publication: PubMed 30679288Favrais G, Ursino M, Mouchel C, Boivin E, Jullien V, Zohar S, Saliba E. Levetiracetam optimal dose-finding as first-line treatment for neonatal seizures occurring in the context of hypoxic-ischaemic encephalopathy (LEVNEONAT-1): study protocol of a phase II trial. BMJ Open. 2019 Jan 24;9(1):e022739. doi: 10.1136/bmjopen-2018-022739.
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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.
Geraldine Favrais, Dr study chair
University Hospital of Tours
Geraldine FAVRAIS, Dr principal investigator
University hospital of Tours
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intravenous Levetiracetam in people with Neonatal Seizures, run by University Hospital, Tours at 8 sites in France.
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 7 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 30 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in France. 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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Levetiracetam Efficacy on EEG recording (time frame: the period just before the LEV loading dose (from 20 min to 3 hours) and the 3 hour time-interval from 1 hour 15 min (T11/4) to 4 hours 15 min (T41/4) after the starting of loading dose infusion (T0)). The study lists 3 primary outcomes in all. 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 NCT02229123, which also lists 1 linked publication.
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 30 Dec 2025.