A Dose Escalation Study of Levetiracetam in the Treatment of Neonatal Seizures

NCT ID: NCT05610085

Last Updated: 2025-10-31

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

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

133 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-24

Study Completion Date

2027-12-31

Brief Summary

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The main purpose of this study is to determine the maximum safe tolerated dose of LEV in the treatment of neonatal seizures. Our hypothesis is that optimal dosing of Levetiracetam (LEV) to treat neonatal seizures is significantly greater than 60mg/kg. This study will be an open label dose-escalation, preliminary safety and efficacy study. There will be a randomized control treatment component. Infants recognized as having neonatal seizures or as being at risk of developing seizures will be recruited and started on continuous video EEG monitoring (CEEG). Eligibility will be confirmed and consent will be obtained. In the first 2 phases of the study, neurologists will identify neonates with mild-moderate seizure burden (less than 8 minutes cumulative seizure activity per hour), appropriate for study with LEV, and exclude patients with higher seizure burden where treatment with PHB is more appropriate. Phase 3 of the dose escalation will only proceed if additional efficacy of LEV has been demonstrated in phases 1 and 2. In Phase 3 we will recruit neonates with seizures of greater severity up to 30 minute seizure burden/hour. This will make the final results of study more generalizable.

If seizures are confirmed, enrolled subjects will receive 60mg/kg of LEV. Subjects whose seizures persist or recur 15 minutes after the first infusion is complete, subjects will then be randomized in the dose escalation study. Patients in the dose escalation study will be randomly assigned to receive either higher dose LEV or treatment with the control drug PHB in a 3:1 allocation ratio, stratified by site.

Funding Source- FDA OOPD

Detailed Description

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Aims/Hypotheses:

Primary Aim: To determine the recommended maximal safe dose of LEV in the setting of neonatal seizures of mild to moderate severity.

If 60mg/kg LEV does not control seizures, subjects will be randomised to receive either additional LEV or PHB. LEV dose will be escalated in 30mg/kg increments to a maximal dose of 150mg/kg total loading dose. We will use a continual reassessment method to determine the maximal safe and tolerated dose.

Secondary/exploratory aims:

* To study the pharmacokinetics of high dose LEV in neonates with seizures of mild to moderate severity.
* To estimate the additional efficacy of higher doses of LEV in neonates with seizures of mild to moderate severity.
* To improve technologies for the prompt detection of neonatal seizures: We will assess the latest version of Persyst's neonatal seizure detector.

Research Design

This is a Phase IIb, open label dose-escalation, preliminary safety and efficacy study. An active drug treatment control arm (PHB group) is included in the study design. This study is not designed or powered to compare high dose LEV and PHB groups, however, the randomized control group will help with interpretation of adverse events and seizure cessation efficacy seen in the high dose escalation group. This is particularly important because of the high rates of morbidity in neonates with seizures.

24-hour seizure control endpoint: cEEG reviewed by a neurophysiologist will be used for assessing 24-hour seizure control. Treatment will be considered effective in achieving 24-hour seizure control if there is a seizure burden less than 30 seconds in the 24 hours following the dose. Change in seizure burden in 2-hour post treatment period will also be assessed.

Intervention If seizure activity occurs participants will be enrolled and will receive 60mg/kg LEV.

If seizures continue babies will then be randomised to receive either:

* Additional LEV at a higher dose (30 mg/kg, 60 mg/kg, or 90 mg/kg depending on the stage of the study), OR
* PHB at 20-40 mg/kg. Maintenance treatment will continue for 5 days, either IV or orally if baby is tolerating feeds.

LEV discontinuation or addition of PHB: there are multiple criteria for transition to, or addition of, PHB treatment if required for seizure control.

Conditions

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Neonatal Seizure Neonatal Encephalopathy Hypoxic-Ischemic Encephalopathy Seizure Newborn

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

If seizures persist or recur after 60 mg/kg LEV patients will be randomized to receive either dose escalation of levetiracetam or phenobarbital. Randomization will occur in a 3:1 ratio LEv: PHB stratified by site.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose escalation with LEV

Additional LEV at a higher dose (30 mg/kg, 60 mg/kg, or 90 mg/kg depending on the stage of the study).

Group Type EXPERIMENTAL

Levetiracetam Injection

Intervention Type DRUG

Neonates will be treated with intravenous levetiracetam 60mg/kg for first line management of seizures, and if seizures persist will be randomized to receive higher dose Levetiracetam or standard of care phenobarbital

Standard of care Phenobarbital

Treatment with Phenobarbital 20mg/kg IV and if needed a further 20mg/kg totalling 40mg/kg

Group Type ACTIVE_COMPARATOR

Phenobarbital Sodium Injection

Intervention Type DRUG

Standard of care for neonatal seizures

Interventions

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Levetiracetam Injection

Neonates will be treated with intravenous levetiracetam 60mg/kg for first line management of seizures, and if seizures persist will be randomized to receive higher dose Levetiracetam or standard of care phenobarbital

Intervention Type DRUG

Phenobarbital Sodium Injection

Standard of care for neonatal seizures

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* at risk for seizures or suspected to be having seizures;
* all seizure aetiologies except correctable metabolic abnormalities such as hypoglycaemia and hypocalcaemia;
* Term neonates (corrected gestational age between 35 and 44 weeks, postnatal age less than 28 days);
* weight \> 2200g.
* Parental ability to comprehend and provide written informed consent

Exclusion Criteria

* Cumulative seizure burden of 8 minutes/ hour or more in phases 1 and 2, Cumulative seizure burden of 30 minutes/hour or more in phase 3;
* Renal failure defined as anuria in the first 24 hours of life;
* Subjects in whom death seems imminent;
* Seizures caused by correctable metabolic abnormality, such as hypocalcaemia, hypoglycaemia.
Maximum Eligible Age

1 Month

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Minnesota

OTHER

Sponsor Role collaborator

Rady Children's Hospital, San Diego

OTHER

Sponsor Role collaborator

Auckland City Hospital

OTHER_GOV

Sponsor Role collaborator

University of Auckland, New Zealand

OTHER

Sponsor Role collaborator

Middlemore Hospital, New Zealand

OTHER

Sponsor Role collaborator

University of California, San Diego

OTHER

Sponsor Role lead

Responsible Party

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Richard H. Haas

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sonya G Wang, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Cynthia M Sharpe, M.D.

Role: PRINCIPAL_INVESTIGATOR

Auckland City Hospital

Jeff J Gold, M.D. PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Richard H Haas, MBBChir

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

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University of California, San Diego

San Diego, California, United States

Site Status RECRUITING

University of Minnesota

Minneapolis, Minnesota, United States

Site Status RECRUITING

Auckland City Hospital

Auckland, Auckland, New Zealand

Site Status RECRUITING

Middlemore Hospital

Auckland, Auckland, New Zealand

Site Status RECRUITING

Capital and Coast District Health Board, Te Whatu Ora, Health New Zealand

Wellington, Wellington Region, New Zealand

Site Status RECRUITING

Countries

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United States New Zealand

Central Contacts

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Sonya G Wang, M.D.

Role: CONTACT

612-301-1454

Brittany Faanes, MPH

Role: CONTACT

612-625-5929

Facility Contacts

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Jeff Gold, M.D.

Role: primary

Brittany Faanes, MPH

Role: primary

612-625-5929

Elizabeth Ramey, MS

Role: backup

Cynthia Sharpe, MBChB

Role: primary

021924015

Chris McKinlay, MBChB

Role: primary

+64274725099

Cynthia Sharpe, MBChB

Role: backup

+6421924015

Krishna Raghu, MBBS, DCH, FRACP

Role: primary

+64 22 309 8900

Other Identifiers

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FD-R-6335

Identifier Type: -

Identifier Source: org_study_id

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