A Pilot Study of NSICU Assessment of Seizure Prophylaxis With Lacosamide

Study Overview
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Brief Summary
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Trial to determine if seizure prophylaxis with IV LCM in NSICU patients experiencing mental status changes due to severe traumatic brain injury (sTBI) will result in improved short- and long-term outcomes and better immediate adverse effects when compared to the current standard of care anticonvulsant (IV fPHT) and will be at least as effective as IV fPHT in preventing clinical and sub-clinical seizure activity.

Detailed Description
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The goals are to compare IV LCM and IV fPHT for seizure prophylaxis in the neuro-critical care setting in terms of the following outcome measures: The short- and long-term incidence of adverse events related to the anticonvulsant medication The frequency of clinically-evident and sub-clinical seizures, as demonstrated by continuous EEG monitoring for the first three days and by clinical assessment for up to 6 months after initial admission. Intermediate and long-term outcomes as measured by standard outcome measures including Extended Glasgow Outcome Scale, Disability Rating Scale, and Resource Utilization Questionnaire

Official Title
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A Pilot Study of NSICU Assessment of Seizure Prophylaxis With Lacosamide

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Drug: lacosamide
* Drug: Fosphenytoin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject with traumatic brain injury admitted to the hospital less than 24 hours prior to randomization GCS score 3-8 (inclusive) or GCS motor score of 5 or less and abnormal admission CT scan showing intracranial pathology Hemodynamically stable with a systolic BP > 90 mmHg At least one reactive pupil Age at least 18 years Signed informed consent and HIPAA authorization for research form Patients will not be excluded because of race, gender, educational status or occupation Exclusion Criteria: No venous access Spinal cord injury History of or CT confirmation of previous brain injury such as brain tumor, cerebral infarct, or spontaneous intracerebral hemorrhage Hemodynamically unstable Suspected anoxic events Other peripheral trauma likely to result in liver failure Age less than 18 years of age Known hypersensitivity to any anticonvulsant Any treatment, condition, or injury that contraindicates treatment with Lacosamide (LCM) or fos-phenytoin (fPHT) Inability to obtain signed informed consent or HIPAA authorization for research

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV LCM (lacosamide)<br>Patients with severe traumatic brain injury (TBI) or subarachanoid hemorrhage (SAH) randomized to seizure prophylaxis with either lacosamide. | Drug: lacosamide<br>* 200 mg IV over 60 minutes; these patients will then be started on a maintenance dose 100 mg, IV BID as prophylaxis administered as per pharmacy protocol consistent with acceptable standards of care for 7 days. The Lacosamide dose can be adjusted as needed if seizures occur for therapeutic effect up to 200 mg bid (400 mg/d) as a maximum dose.<br>* Other names: Vimpat;|
| Active Comparator: IV fPHT (fos-phenytoin)<br>Patients with TBI or SAH randomized to seizure prophylaxis with fos-phenytoin | Drug: Fosphenytoin<br>* 20 mgPE/kg IV over 60 minutes and then will be started on a maintenance dose (5 mgPE/kg/day, rounded to nearest dose of 150 mgPE IV, BID administered as per pharmacy protocol consistent with acceptable standards of care for 7 days<br>* Other names: Dilantin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events | The primary outcome measure is the incidence of clinical adverse events. These will be followed by daily clinical observations during the hospital stay. Subjects will be evaluated for e.g., seizures, fever, neurological changes, cardiovascular, hematologic and dermatologic abnormalities, liver failure, renal failure, and death; EKGs will be requested as per ICU routines through day 7. | baseline to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Seizures | Number of seizures in the first 72 hours based on EEG recording | baseline to 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lacosamide, Fosphenytoin, traumatic brain injury, Glasgow coma scale, Disability Rating Scale, Resource Utilization Questionnaire, Continuous EEG, seizures