A Pilot Study of NSICU Assessment of Seizure Prophylaxis With Lacosamide

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01110187
• Collaborator: UCB Pharma (Industry)
• Enrollment: 11
• Locations: 3
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Traumatic Brain Injury	Drug: lacosamide; Drug: Fosphenytoin	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Pilot Study of NSICU Assessment of Seizure Prophylaxis With Lacosamide
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Number of Participants With Seizures [baseline to 72 hours]

   Number of seizures in the first 72 hours based on EEG recording

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UC Health University Pointe	Cincinnati	Ohio	United States	45069
2	UC Health Medical Arts Building	Cincinnati	Ohio	United States	45219
3	University Hospital	Cincinnati	Ohio	United States	45219

Sponsors and Collaborators

• University of Alabama at Birmingham
• UCB Pharma

Investigators

• Principal Investigator: Jerzy P Szaflarski, M.D., PhD, Univeristy of Cincinnati

Study Documents (Full-Text)

None provided.

More Information

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.

• Responsible Party: Jerzy P Szaflarski, Professor, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT01110187
• Other Study ID Numbers: JPS-001
• First Posted: Apr 26, 2010
• Last Update Posted: Apr 28, 2014
• Last Verified: Feb 1, 2014

• Keywords provided by Jerzy P Szaflarski, Professor, University of Alabama at Birmingham: Lacosamide; Fosphenytoin; traumatic brain injury; Glasgow coma scale; Disability Rating Scale; Resource Utilization Questionnaire; Continuous EEG; seizures
• Additional relevant MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Seizures; Lacosamide; Fosphenytoin

Study Results

Participant Flow

Arm/Group Title	IV LCM	IV fPHT
Arm/Group Description	Patients with severe TBI later randomized to seizure prophylaxis with LCM (Lacosamide). For IV LCM dosing and adjustment see "Intervention" section.	Patients randomized to fPHT (fos-phenytoin) with moderate or severe TBI. For IV fPHT dosing and adjustment see "Intervention" section.
Period Title: Overall Study
STARTED	7	4
COMPLETED	7	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	IV LCM	IV fPHT	Total
Arm/Group Description	patients randomized to IV LCM (7)	patients randomized to IV fPHT (4)	Total of all reporting groups
Overall Participants	7	4	11
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57	55.5	56
Sex: Female, Male (Count of Participants)
Female	3 42.9%	0 0%	3 27.3%
Male	4 57.1%	4 100%	8 72.7%

Outcome Measures

1. Primary Outcome

Title	Number of Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

all participants in each arm were available for analyses

Arm/Group Title	IV LCM	IV fPHT
Arm/Group Description	Patients with severe TBI later randomized to seizure prophylaxis with lacosamide.	Patients with severe TBI randomized to seizure prophylaxis with fPHT
Measure Participants	7	4
Number [number of events experienced]	12	21

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV LCM	IV fPHT
Arm/Group Description	Patients with severe traumatic brain injury (TBI) or subarachanoid hemorrhage (SAH) randomized to seizure prophylaxis with either lacosamide. 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.	Patients with TBI or SAH randomized to seizure prophylaxis with fos-phenytoin 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
Measure Participants	7	4
Number [number of participants with seizures]	0 0%	0 0%

Adverse Events

Time Frame	baseline to 7 days
Arm/Group Title	IV LCM		IV fPHT
Arm/Group Description	Patients with severe TBI later randomized to seizure prophylaxis with lacosamide.		Patients with severe TBI later randomized to seizure prophylaxis with phenytoin.
All Cause Mortality
	IV LCM		IV fPHT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IV LCM		IV fPHT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/7 (28.6%)		0/4 (0%)
Nervous system disorders
death	2/7 (28.6%)	2	0/4 (0%)	0
Other (Not Including Serious) Adverse Events
	IV LCM		IV fPHT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/7 (100%)		4/4 (100%)
Blood and lymphatic system disorders
anemia	2/7 (28.6%)	2	2/4 (50%)	2
low platelets	2/7 (28.6%)	2	2/4 (50%)	2
Cardiac disorders
arrythmia	1/7 (14.3%)	1	3/4 (75%)	3
Hepatobiliary disorders
LFT	1/7 (14.3%)	1	3/4 (75%)	3
Investigations
fever	3/7 (42.9%)	3	3/4 (75%)	3
Hypotension	0/7 (0%)	0	1/4 (25%)	1
Nervous system disorders
increased ICP	0/7 (0%)	0	3/4 (75%)	3
stroke	1/7 (14.3%)	1	3/4 (75%)	3
Skin and subcutaneous tissue disorders
skin reaction	0/7 (0%)	0	1/4 (25%)	1

Limitations/Caveats

Early termination due to lack of enrollment. Statistical comparisons between groups are not possible and were not performed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.