Comparative Trial of IV Lacosamide Versus Phenytoin for Seizure Management

Study Overview
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Brief Summary
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The Investigator plans to perform a prospective, randomized, single blinded, study that will compare patients treated with IV lacosamide to those treated with Phenytoin in the Intensive Care Unit (ICU) setting. The investigator will also evaluate the rate of clinically evident and sub-clinical seizures, and to compare long-term outcomes between patients treated with lacosamide and those treated with Phenytoin.

Official Title
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Prospective, Randomized, Single-blinded Comparative Trial of IV Lacosamide Versus Phenytoin for Seizure Management

Conditions
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Seizures

Intervention / Treatment
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* Drug: lacosamide
* Drug: Phenytoin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Traumatic Brain Injury (TBI) or Subarachnoid hemorrhage (SAH) Admitted to the hospital less than 48 hours prior to randomization Glasgow Coma Scale (GCS) score 3-8 (inclusive), or GCS motor score of five or less and abnormal CT scan showing intracranial pathology Hemodynamically stable Older than 18 years of age Exclusion Criteria: No IV access Spinal cord injury History of or CT confirmation of previous brain injury, including brain tumor, stroke, or a spontaneous intracerebral hemorrhage Hemodynamically unstable Suspected anoxia Liver failure Younger than 18 years of age Pregnant Allergy to phenytoin or lacosamide Inability to obtain consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lacosamide<br>The lacosamide group will receive a loading dose of 400 mg IV, and on maintenance dose of up to 400 mg every 12 hours. | Drug: lacosamide<br>* Comparison of patients treated with IV lacosamide to those treated with phenytoin in the intensive care unit setting. The lacosamide group will receive a loading dose of 400 mg IV, and on maintenance dose of up to 400 mg every 12 hours.<br>* Other names: Vimpat;|
| Active Comparator: phenytoin<br>the phenytoin group will receive a loading dose of 20 mg/K IV, maximum of 2000 mg, given over 60 min. and will be started on a maintenance dose of 5 mg/K/day. Levels will be checked accordingly. | Drug: Phenytoin<br>* the phenytoin group will receive a loading dose of 20 mg/K IV, maximum of 2000 mg, given over 60 min. and will be started on a maintenance dose of 5 mg/K/day.<br>* Other names: Dilantin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Clinical Adverse Events | Safety: the primary outcome measure will be the incidence of clinical adverse events. Patients will be evaluated daily during the hospital stay for seizures, fever, neurological changes, cardiovascular, hematologic and dermatologic abnormalities, liver failure, renal failure, and death. Each adverse event will be classified by the principal investigator as attributable or possibly attributable to the study drug versus other events. Serious adverse events for these to study will be defined as those that result in death, prolonged hospitalization, life threatening events, persistent or significant disability, or an important medical event that may not be immediately life threatening or result in death but based upon appropriate medical judgment may jeopardize the participant, or may require medical or surgical intervention to prevent one of the other outcomes listed. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | Efficacy: the secondary endpoints will be seizure frequency and long-term outcomes (measure by disability scales). All patients will be monitored on continuous EEG for 72 hours or until a week and following commands. Since over 50% of initial seizure activity in these patients are usually subclinical as reported in the finished studies, and about 90% of the seizures happen within the first two days of admission to the ICU, the investigator would stop EEG recordings once patient awake, or by 72 hours after admission if there were no seizures. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lacosamide, phenytoin