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

NCT05610085 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: FD-R-6335
• Study Type: interventional
• Target: 133
• Locations: 2 countries
• Sites: 5

Brief Summary

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

Conditions

Neonatal Seizure; Neonatal Encephalopathy; Hypoxic-Ischemic Encephalopathy; Seizure Newborn

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is the maximum safe and tolerated dose of Levetiracetam

  A continual reassessment method will be used to determine the maximal safe and tolerated dose

  4 years

Secondary Outcomes (7)

• Levetiracetam CL

  4 years

• Levetiracetam Vd

  4 years

• Adverse event rates

  4 years

• Long-term outcome

  8 years

• Seizure burden reduction

  4 years

Study Arms (2)

Dose escalation with LEV

EXPERIMENTAL

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

Drug: Levetiracetam Injection

Standard of care Phenobarbital

ACTIVE COMPARATOR

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

Drug: Phenobarbital Sodium Injection

Interventions

Levetiracetam Injection 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

Dose escalation with LEV

Phenobarbital Sodium Injection DRUG

Standard of care for neonatal seizures

Standard of care Phenobarbital

Eligibility Criteria

• Age: Up to 1 Month
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Diego: lead
• University of Minnesota: collaborator
• Rady Children's Hospital, San Diego: collaborator
• Auckland City Hospital: collaborator
• University of Auckland, New Zealand: collaborator
• Middlemore Hospital, New Zealand: collaborator

Study Sites (5)

University of California, San Diego

San Diego, California, 92093, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

Auckland City Hospital

Auckland, Auckland, 1023, New Zealand

RECRUITING

Middlemore Hospital

Auckland, Auckland, 1050, New Zealand

RECRUITING

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

Wellington, Wellington Region, 6021, New Zealand

RECRUITING

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain

Interventions

Levetiracetam; Phenobarbital

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Barbiturates; Pyrimidinones; Pyrimidines

Study Officials

• Sonya G Wang, M.D.

  University of Minnesota

  PRINCIPAL INVESTIGATOR

• Cynthia M Sharpe, M.D.

  Auckland City Hospital

  PRINCIPAL INVESTIGATOR

• Jeff J Gold, M.D. PhD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

• Richard H Haas, MBBChir

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sonya G Wang, M.D.

CONTACT

612-301-1454; sgwang@umn.edu

Brittany Faanes, MPH

CONTACT

612-625-5929; grego318@umn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: October 27, 2022
• First Posted: November 9, 2022
• Study Start: March 24, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: October 31, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (3); US (2)