Traumatic Brain Injury
Conditions
Keywords
Lacosamide, Fosphenytoin, traumatic brain injury, Glasgow coma scale, Disability Rating Scale, Resource Utilization Questionnaire, Continuous EEG, seizures
Brief summary
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
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
Interventions
DRUGlacosamide
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.
DRUGFosphenytoin
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
Sponsors
UCB Pharma
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events | baseline to 7 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Seizures | baseline to 72 hours | Number of seizures in the first 72 hours based on EEG recording |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IV LCM patients randomized to IV LCM (7) | 7 |
| IV fPHT patients randomized to IV fPHT (4) | 4 |
| Total | 11 |
Baseline characteristics
| Characteristic | IV LCM | IV fPHT | Total |
|---|---|---|---|
| Age, Continuous | 57 years | 55.5 years | 56 years |
| Sex: Female, Male Female | 3 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 4 / 4 |
| serious Total, serious adverse events | 2 / 7 | 0 / 4 |
Outcome results
Primary
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.
Time frame: baseline to 7 days
Population: all participants in each arm were available for analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV LCM | Number of Adverse Events | 12 number of events experienced |
| IV fPHT | Number of Adverse Events | 21 number of events experienced |
Secondary
Number of Participants With Seizures
Number of seizures in the first 72 hours based on EEG recording
Time frame: baseline to 72 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV LCM | Number of Participants With Seizures | 0 number of participants with seizures |
| IV fPHT | Number of Participants With Seizures | 0 number of participants with seizures |