Hypoxic-Ischemic Encephalopathy Clinical Trial
— NEOLEV3Official title:
A Phase IIb Dose Escalation Study of Levetiracetam for the Treatment of Neonatal Seizures
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
Status | Recruiting |
Enrollment | 133 |
Est. completion date | December 31, 2027 |
Est. primary completion date | July 1, 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A to 1 Month |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
New Zealand | Auckland City Hospital | Auckland | |
New Zealand | Middlemore Hospital | Auckland | |
United States | University of Minnesota | Minneapolis | Minnesota |
United States | University of California, San Diego | San Diego | California |
Lead Sponsor | Collaborator |
---|---|
University of California, San Diego | Auckland City Hospital, Middlemore Hospital, New Zealand, Rady Children's Hospital, San Diego, University of Auckland, New Zealand, University of Minnesota |
United States, New Zealand,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Levetiracetam CL | Population pharmacokinetic parameters for LEV Clearance (CL)will be calculated | 4 years | |
Secondary | Levetiracetam Vd | Population pharmacokinetic parameters for LEV Volume of distribution (Vd) will be calculated | 4 years | |
Secondary | Adverse event rates | Rates of adverse events seen with high dose LEV treatment will be reported and compared to rates seen in PHB control arm. | 4 years | |
Secondary | Long-term outcome | Rates of adverse long-term outcome ( Death or Disability at 24 months) will be compared between treatment arms | 8 years | |
Secondary | Seizure burden reduction | Number of patients with at least 50% seizure burden reduction post treatment will be compared between randomized treatment arms | 4 years | |
Secondary | Seizure freedom rates | Number of patients who become seizure free for 24 hours post treatment will be compared between the randomized treatment groups in each stage of the study | 4 years | |
Secondary | Estimate of efficacy of higher dose LEV | Assuming no dose limiting toxicity is demonstrated and the study proceeds to completion, 50 subjects will be treated at 120mg/kg or higher dosing level. This sample size will give satisfactory power for estimating additional efficacy of higher doses. For example, if we document an additional response rate of 15%, this sample size will provide a 95% confidence interval (0.051, 0.248) around that estimate. | 4 years |
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