Levetiracetam Treatment of Neonatal Seizures: Safety and Efficacy Phase II Study

NCT ID: NCT02229123

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-27

Study Completion Date

2022-02-23

Brief Summary

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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

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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

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Neonatal Seizures

Keywords

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seizures neonates anticonvulsant treatment levetiracetam hypoxic-ischemic encephalopathy electroencephalography

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Intravenous levetiracetam

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.

Group Type EXPERIMENTAL

Intravenous Levetiracetam

Intervention Type DRUG

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.

Interventions

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Intravenous Levetiracetam

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

36 Weeks

Maximum Eligible Age

43 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role collaborator

Rennes University Hospital

OTHER

Sponsor Role collaborator

Amiens University Hospital

OTHER

Sponsor Role collaborator

University Hospital, Tours

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Geraldine Favrais, Dr

Role: STUDY_CHAIR

University Hospital of Tours

Geraldine FAVRAIS, Dr

Role: PRINCIPAL_INVESTIGATOR

University hospital of Tours

Locations

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Service de réanimation néonatale

Angers, , France

Site Status

Service de réanimation néonatale

Lille, , France

Site Status

Service de réanimation et service néonatale

Orléans, , France

Site Status

Service de réanimation néonatale et pédiatrique

Paris, , France

Site Status

Service de réanimation néonatale

Reims, , France

Site Status

Néonatologie

Rennes, , France

Site Status

Service de Pédiatrie néonatale et réanimation

Rouen, , France

Site Status

Service de Néonatologie

Tours, , France

Site Status

Countries

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France

References

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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.

Reference Type RESULT
PMID: 30679288 (View on PubMed)

Other Identifiers

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2014-000791-26

Identifier Type: -

Identifier Source: org_study_id