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

NCT02229123 | Completed Phase 2 DMC

• 1 other identifier: 2014-000791-26
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 8

Brief 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 with seizures in hypoxic-ischemic encephalopathy context. This new anticonvulsivant drug is a promising treatment for seizures in newborns.

Conditions

Neonatal Seizures

Keywords

seizures; neonates; anticonvulsant treatment; levetiracetam; hypoxic-ischemic encephalopathy; electroencephalography

Outcome Measures

Primary Outcomes (3)

• Levetiracetam Efficacy on EEG recording

  Efficacy has been defined as an 80% reduction of seizure burden on EEG recording.

  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.

  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.

  30 days from the loading dose

Secondary Outcomes (7)

• Levetiracetam Elimination Clearance

  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

  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

  30 min, 4 hours and 7 hours after the end of Levetiracetam loading dose infusion

• Levetiracetam Loading Dose Area under Curve

  30 min, 4 hours and 7 hours after the end of Levetiracetam loading dose infusion

• Levetiracetam Entire Treatment Area Under Curve

  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.

Study Arms (1)

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.

Drug: Intravenous Levetiracetam

Interventions

Intravenous Levetiracetam 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.

Intravenous levetiracetam

Eligibility Criteria

• Age: 36 Weeks - 43 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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
• Participation to an interventional research study

Sponsors & Collaborators

• University Hospital, Tours: lead
• Assistance Publique - Hôpitaux de Paris: collaborator
• Rennes University Hospital: collaborator
• Amiens University Hospital: collaborator

Study Sites (8)

Service de réanimation néonatale

Angers, 49000, France

Location

Service de réanimation néonatale

Lille, 59037, France

Location

Service de réanimation et service néonatale

Orléans, 45100, France

Location

Service de réanimation néonatale et pédiatrique

Paris, 75012, France

Location

Service de réanimation néonatale

Reims, 51092, France

Location

Néonatologie

Rennes, 35000, France

Location

Service de Pédiatrie néonatale et réanimation

Rouen, 76031, France

Location

Service de Néonatologie

Tours, 37 000, France

Location

Related Publications (1)

• 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.

  PMID: 30679288 RESULT

MeSH Terms

Conditions

Seizures; Hypoxia-Ischemia, Brain

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory

Study Officials

• Geraldine Favrais, Dr

  University Hospital of Tours

  STUDY CHAIR

• Geraldine FAVRAIS, Dr

  University hospital of Tours

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 27, 2014
• First Posted: August 29, 2014
• Study Start: February 27, 2018
• Primary Completion: February 23, 2022
• Study Completion: February 23, 2022
• Last Updated: December 30, 2025

Record last verified: 2025-12

Locations

FR (8)