Intravenous Lacosamide Compared With Fosphenytoin in the Treatment of Patients With Frequent Nonconvulsive Seizures - Full Text View

Purpose

This a phase 2 study comparing the efficacy of intravenous (IV) lacosamide (LCM) with IV fosphenytoin (fPHT) in controlling frequent nonconvulsive seizures (NCSs), the Adverse Events profile of LCM compared with fPHT when used to treat frequent NCSs, and length of stay in an intensive care unit for subjects treated with LCM versus subjects treated with fPHT. The trial will include a preacute-treatment period, an acute-treatment period, a postacute-treatment period, and a long-term follow-up period.

Condition	Intervention	Phase
Nonconvulsive Seizures	Drug: Lacosamide - 'Crossover' Drug: Fosphenytoin - 'crossover'	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Single Blind (Investigator) Primary Purpose: Treatment
Official Title:	Utility of Intravenous Lacosamide Compared With Fosphenytoin in the Treatment of Patients With Frequent Nonconvulsive Seizures

Resource links provided by NLM:

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Seizures

Drug Information available for: Fosphenytoin sodium Fosphenytoin Lacosamide

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:

Percentage of subjects who experience no NCSs for 24 hours following treatment with LCM vs. fPHT, as measured by continuous electroencephalography (cEEG) monitoring. [ Time Frame: 26-68 hours ] [ Designated as safety issue: Yes ]
Percentage of subjects who experience no NCSs for 24 hours following treatment with LCM vs. fPHT, as measured by cEEG monitoring.

Secondary Outcome Measures:

Percentage of subjects who require a rebolus of the initial antiepileptic drug (AED) to control NCSs in the LCM vs fPHT arms. [ Time Frame: 26-68 hours ] [ Designated as safety issue: Yes ]
Percentage of subjects who require a rebolus of the initial AED to control NCSs in the LCM vs fPHT arms.
Percentage of subjects who require a second AED to control NCSs. [ Time Frame: 26-68 hours ] [ Designated as safety issue: Yes ]
Percentage of subjects who require a second AED to control NCSs.
Percent change in seizure time (defined as the number of minutes of electrographic seizure (ESz) activity per hour) before treatment and at the end of the first treatment arm. [ Time Frame: 26-68 hours ] [ Designated as safety issue: Yes ]
Percent change in seizure time (defined as the number of minutes of ESz activity per hour) before treatment and at the end of the first treatment arm.
Percent change in seizure time (defined as the number of minutes of ESz activity per hour) before treatment and at the end of the second treatment arm. [ Time Frame: 26-68 hours ] [ Designated as safety issue: Yes ]
Percent change in seizure time (defined as the number of minutes of ESz activity per hour) before treatment and at the end of the second treatment arm.
Time from bolus to time of the end of the last seizure for both first (initial bolus/rebolus)and second (crossover bolus/rebolus) treatment arms. [ Time Frame: 26-68 hours ] [ Designated as safety issue: Yes ]
Time from bolus to time of the end of the last seizure for both first (initial bolus/rebolus)and second (crossover bolus/rebolus) treatment arms.
Frequency of predefined adverse events (AEs) in the LCM vs fPHT arms. [ Time Frame: 26-68 hours ] [ Designated as safety issue: Yes ]
Frequency of predefined AEs in the LCM vs fPHT arms.
Percentage of subjects in whom study drug is withdrawn early [ Time Frame: 26-68 hours ] [ Designated as safety issue: Yes ]
Percentage of subjects in whom study drug is withdrawn early
Days in the intensive care unit/hospital from start of treatment in the LCM vs fPHT arms. [ Time Frame: 26-68 hours ] [ Designated as safety issue: Yes ]
Days in the intensive care unit/hospital from start of treatment in the LCM vs fPHT arms.
Functional status as measured by the Functional Disability Scale at Day 7 to 9 postrandomization and Day 30 post-randomization in the LCM vs fPHT arms. [ Time Frame: 7-32 Days ] [ Designated as safety issue: Yes ]
Functional status as measured by the Functional Disability Scale at Day 7 to 9 postrandomization and Day 30 post-randomization in the LCM vs fPHT arms.
Percentage of all subjects who have had a seizure, are on AED therapy, and are alive/dead at the 6-, 12-, and 24-month post-randomization follow-ups. [ Time Frame: 6-24 months ] [ Designated as safety issue: No ]
Percentage of all subjects who have had a seizure, are on AED therapy, and are alive/dead at the 6-, 12-, and 24-month post-randomization follow-ups.

Estimated Enrollment:	200
Study Start Date:	May 2012
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: fPHT fPHT treatment arm, a bolus of 20 mg PE/kg will be administered at a rate of no greater than 75 mg PE/minute. If a further bolus is required, 5 mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5 mg PE/kg divided into 2 doses.	Drug: Lacosamide - 'Crossover' If any of the following occurs, the subject will have reached the end of the first treatment arm and will "cross over" and begin receiving the other drug, ie, the one not originally administered: The subject subsequently has another seizure within 24 hours following the 2-hour post-rebolus observation-only period. The subject does not receive a rebolus but has a seizure within 24 hours following the 2 hour post-bolus observation-only period. The subject experiences an AE that precludes further use of the first study drug. If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period, rebolusing (if necessary), and study assessments with the second drug, beginning with the Baseline assessments. Other Name: Vimpat
Experimental: LCM LCM treatment arm, a bolus of 400 mg will be administered over 30 minutes. If a further bolus is required, 200 mg will be administered. Regardless of whether the subject received a rebolus, he or she will begin receiving a maintenance dose 12 hours after the initial dose. The daily maintenance dose will be the same as the total bolus (400 mg or 600 mg) divided into 2 doses.	Drug: Fosphenytoin - 'crossover' If any of the following occurs, the subject will have reached the end of the first treatment arm and will "cross over" and begin receiving the other drug, ie, the one not originally administered: The subject subsequently has another seizure within 24 hours following the 2-hour post-rebolus observation-only period. The subject does not receive a rebolus but has a seizure within 24 hours following the 2 hour post-bolus observation-only period. The subject experiences an AE that precludes further use of the first study drug. If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period, rebolusing (if necessary), and study assessments with the second drug, beginning with the Baseline assessments.

Arms

Assigned Interventions

Active Comparator: fPHT

fPHT treatment arm, a bolus of 20 mg PE/kg will be administered at a rate of no greater than 75 mg PE/minute. If a further bolus is required, 5 mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5 mg PE/kg divided into 2 doses.

Drug: Lacosamide - 'Crossover'

If any of the following occurs, the subject will have reached the end of the first treatment arm and will "cross over" and begin receiving the other drug, ie, the one not originally administered:

The subject subsequently has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.
The subject does not receive a rebolus but has a seizure within 24 hours following the 2 hour post-bolus observation-only period.
The subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period, rebolusing (if necessary), and study assessments with the second drug, beginning with the Baseline assessments.

Other Name: Vimpat

Experimental: LCM

LCM treatment arm, a bolus of 400 mg will be administered over 30 minutes. If a further bolus is required, 200 mg will be administered. Regardless of whether the subject received a rebolus, he or she will begin receiving a maintenance dose 12 hours after the initial dose. The daily maintenance dose will be the same as the total bolus (400 mg or 600 mg) divided into 2 doses.

Drug: Fosphenytoin - 'crossover'

If any of the following occurs, the subject will have reached the end of the first treatment arm and will "cross over" and begin receiving the other drug, ie, the one not originally administered:

The subject subsequently has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.
The subject does not receive a rebolus but has a seizure within 24 hours following the 2 hour post-bolus observation-only period.
The subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period, rebolusing (if necessary), and study assessments with the second drug, beginning with the Baseline assessments.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Have the capacity to understand and sign an institutional review board (IRB)-approved informed consent form (ICF) or have a legally authorized representative (LAR) available to sign on behalf of the subject.
Are undergoing cEEG monitoring in the neurologic intensive care unit (NICU) or other closely monitored environment.
Are experiencing NCSs according to the following criteria:
- At least 1 ESz lasting at least 10 seconds, with or without clinical correlates, occurring within the last 6 hours of cEEG monitoring.
- If a new AED has been started, ESzs must have occurred per the preceding bullet point at least 2 hours after starting that AED.
- If individual ESzs are not well defined, ESz time is at least 10 seconds and less than 30 minutes per hour of cEEG recording.
Are being considered for treatment with an IV AED.
Are at least 18 years old.

Exclusion Criteria:

Treatment with PHT, fPHT, or LCM in the last 7 days.
Contraindication for the use of fPHT or LCM.
Ongoing generalized convulsive status epilepticus (SE) (more than 2 generalized tonic-clonic seizures within 30 minutes without recovery to baseline or 1 seizure lasting longer than 10 minutes).
Episodes of SE, defined as at least 30 minutes of ESz activity in 1 hour, in the last 6 hours.
Encephalopathic event secondary to acute anoxic/hypoxic event.
Undergoing therapeutic hypothermia protocol.
Continuous EEG monitoring showing only periodic discharges or rhythmic delta activity without clear ESzs (for definitions of periodic discharges, rhythmic delta activity, and ESzs, see the Manual of Operations).
Electroencephalographic seizures consistent with typical absence seizures.
Evaluation for spell characterization or surgical treatment for epilepsy.
Pregnancy.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01458522

Locations

United States, California
Huntington Memorial Hospital	Recruiting
Pasadena, California, United States, 91109
Contact: Sadie Seto 626-397-3882 sadie.seto@huntingtonhospital.com
Principal Investigator: Yafa Minazad, MD
United States, Connecticut
Yale University School of Medicine	Recruiting
New Haven, Connecticut, United States, 06520
Contact: Jennifer Bonito 203-785-3638 jennifer.bonito@yale.edu
Principal Investigator: Lawrence Hirsch, MD
United States, Georgia
Emory University School of Medicine	Recruiting
Atlanta, Georgia, United States, 30307
Contact: Melanie Newman 404-778-4249 mnewma2@emory.edu
Principal Investigator: Suzette LaRoche, MD
United States, Massachusetts
Beth Israel Deaconess Medical Center	Recruiting
Boston, Massachusetts, United States, 02215
Contact: Allison Glasgow 617-667-0324 alglasgo@bidmc.harvard.edu
Principal Investigator: Susan Herman, MD
Brigham and Woman's Hospital	Recruiting
Boston, Massachusetts, United States, 02215
Contact: Nichelle Llewellyn 617-732-5423 NLLEWELLYN@PARTNERS.ORG
Principal Investigator: Jong Lee, MD
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02214
Contact: Samantha Donovan 617-643-4617 SRDONOVAN@partners.org
Principal Investigator: Brandon Westover, MD
United States, North Carolina
Mission Hospital	Recruiting
Asheville, North Carolina, United States, 28801
Contact: Leslie Shell 828-213-7993 leslie.shell@msj.org
Principal Investigator: Jennifer Jones, MD
Duke University Medical Center	Recruiting
Durham, North Carolina, United States, 27710
Contact: Brian Mace 919-684-0081 brian.mace@duke.edu
Principal Investigator: Bradley Kolls, MD
United States, Pennsylvania
University of Pittsburgh Medical Center	Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Sharon DeCesare 412-647-4994 decesx@upmc.edu
Principal Investigator: Maria Baldwin, MD
United States, South Carolina
Medical University of South Carolina	Recruiting
Charleston, South Carolina, United States, 29425
Contact: Ashley Gnatt gantt@musc.edu
Principal Investigator: Jonathan Halford, MD
United States, Tennessee
Vanderbilt University Medical Center	Recruiting
Nashville, Tennessee, United States, 37232
Contact: Melissa Osborn 615-322-8817 melissa.osborn@vanderbilt.edu
Principal Investigator: Amir Arain, MD
United States, Texas
University of Texas Southwestern Medical Center Dallas	Not yet recruiting
Dallas, Texas, United States, 75390-8589
Contact: Jan Cameron-Watts 214-648-0363 jan.cameronwatts@utsouthwestern.edu
Principal Investigator: Puneet Gupta, MD

Sponsors and Collaborators

Aatif Husain

UCB, Inc.

Investigators

Principal Investigator:

Aatif Husain, MD

Duke Clinical Research Institute

More Information

No publications provided

Responsible Party:	Aatif Husain, MD, Duke University Medical Center
ClinicalTrials.gov Identifier:	NCT01458522 History of Changes
Other Study ID Numbers:	Pro00033295, DCRI-CEMC101.01, Pro00037794
Study First Received:	October 20, 2011
Last Updated:	April 17, 2013
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by Duke University:

Nonconvulsive Seizures

Additional relevant MeSH terms:

Seizures
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms

Fosphenytoin
Phenytoin
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 17, 2013

Intravenous Lacosamide Compared With Fosphenytoin in the Treatment of Patients With Frequent Nonconvulsive Seizures (TRENdS)