A Pilot Study of NSICU Assessment of Seizure Prophylaxis With Lacosamide

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.

Study Overview

• Status: Terminated
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Drug: lacosamide; Drug: Fosphenytoin

Detailed Description

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:

1. The short- and long-term incidence of adverse events related to the anticonvulsant medication
2. 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.
3. Intermediate and long-term outcomes as measured by standard outcome measures including Extended Glasgow Outcome Scale, Disability Rating Scale, and Resource Utilization Questionnaire

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University Hospital
    • Cincinnati, Ohio, United States, 45219
      • UC Health Medical Arts Building
    • Cincinnati, Ohio, United States, 45069
      • UC Health University Pointe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IV LCM (lacosamide); Patients with severe traumatic brain injury (TBI) or subarachanoid hemorrhage (SAH) randomized to seizure prophylaxis with either lacosamide.	Drug: lacosamide; 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.; Other Names: Vimpat
Active Comparator: IV fPHT (fos-phenytoin); Patients with TBI or SAH randomized to seizure prophylaxis with fos-phenytoin	Drug: Fosphenytoin; 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; Other Names: Dilantin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: UCB Pharma
• Investigators: Principal Investigator: Jerzy P Szaflarski, M.D., PhD, Univeristy of Cincinnati

Publications and helpful links

General Publications

• Szaflarski JP, Sangha KS, Lindsell CJ, Shutter LA. Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Neurocrit Care. 2010 Apr;12(2):165-72. doi: 10.1007/s12028-009-9304-y.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: April 16, 2010
• First Submitted That Met QC Criteria: April 22, 2010
• First Posted (Estimate): April 26, 2010

Study Record Updates

• Last Update Posted (Estimate): April 28, 2014
• Last Update Submitted That Met QC Criteria: March 26, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: traumatic brain injury; seizures; Lacosamide; Glasgow coma scale; Fosphenytoin; Disability Rating Scale; Resource Utilization Questionnaire; Continuous EEG
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; Seizures; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lacosamide; Fosphenytoin
• Other Study ID Numbers: JPS-001