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

NCT ID: NCT01458522

Last Updated: 2018-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2015-07-31

Brief Summary

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.

Detailed Description

Exploratory, prospective, multicenter, open-label, randomized study, in which the physicians who are interpreting cEEGs for treatment purposes and the central reviewers who are providing final cEEG interpretation for study purposes are all blinded to treatment.

Initial LCM/maintenance doses: Subjects will receive a 400-mg IV initial bolus over 30 minutes, followed by a 2-hour post-dose observation-only period. If a breakthrough seizure occurs in the 6 hours following the 2-hour post-dose observation-only period, the subject will receive a 200-mg rebolus over 30 minutes. Regardless of whether a rebolus was administered, a maintenance dose of LCM will be started 12 hours after the initial bolus, and it will continue every 12 hours throughout the acute-treatment period. The daily maintenance dose will be equivalent to the total IV bolus per day (400 mg if no rebolus was administered or 600 mg if a rebolus was administered), divided into 2 doses. After completion of the acute-treatment period, daily maintenance with an AED will be at the discretion of the treating physician.

Initial fPHT/maintenance doses: Subjects will receive a 20-mg PE/kg IV initial bolus at a rate no greater than 75 mg PE/minute, followed by a 2-hour post-dose observation-only period. If a breakthrough seizure occurs in the 6 hours following the 2-hour post-dose observation-only period, the subject will receive a 5-mg PE/kg IV rebolus at a rate no greater than 75 mg PE/minute. Regardless of whether a rebolus was administered, a maintenance dose of fPHT will be started 12 hours after the initial bolus, and it will continue every 12 hours throughout the acute-treatment period. The daily maintenance dose will be 5 mg PE/kg, divided into 2 doses. After completion of the acute-treatment period, daily maintenance with an AED will be at the discretion of the treating physician.

Crossover/maintenance doses: If a subject does not receive a rebolus but has a seizure within 24 hours following the 2-hour post-initial-dose observation-only period, he or she will "cross over" and begin receiving the other drug, ie, the one not originally administered. If a subject does receive a rebolus and has another seizure within 24 hours following the 2-hour post-rebolus observation-only period, he or she will also cross over to the other drug. If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period and rebolusing, if necessary. If a subject crosses over and starts receiving the second drug, in addition to receiving every-12-hours maintenance doses of the drug originally administered, the subject will also receive maintenance doses of the second drug every 12 hours, beginning 12 hours after the first dose of the second drug.

Conditions

Nonconvulsive Seizures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

fPHT 20mg

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.

Group Type: ACTIVE_COMPARATOR

fPHT

Intervention Type: DRUG

If after initial treatment with fPHT 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.

LCM

Intervention Type: DRUG

If after initial treatment with LCM 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.

LCM 400mg

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.

Group Type: EXPERIMENTAL

fPHT

Intervention Type: DRUG

If after initial treatment with fPHT 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.

LCM

Intervention Type: DRUG

If after initial treatment with LCM 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.

Interventions

fPHT

If after initial treatment with fPHT 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.

Intervention Type: DRUG

LCM

If after initial treatment with LCM 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.

Intervention Type: DRUG

Other Intervention Names

Cerebyx, Fosphenytoin; Vimpat, Lacosamide

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Are undergoing cEEG monitoring in the neurologic intensive care unit (NICU) or other closely monitored environment.

3. 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.

4. Are being considered for treatment with an IV AED.

5. Are at least 18 years old.

Exclusion Criteria

1. Treatment with PHT, fPHT, or LCM in the last 7 days.

2. Contraindication for the use of fPHT or LCM.

3. 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).

4. Episodes of SE, defined as at least 30 minutes of ESz activity in 1 hour, in the last 6 hours.

5. Encephalopathic event secondary to acute anoxic/hypoxic event.

6. Undergoing therapeutic hypothermia protocol.

7. 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).

8. Electroencephalographic seizures consistent with typical absence seizures.

9. Evaluation for spell characterization or surgical treatment for epilepsy.

10. Pregnancy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UCB Pharma

INDUSTRY

Sponsor Role: collaborator

Aatif Husain

OTHER

Sponsor Role: lead

Responsible Party

Aatif Husain

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Aatif Husain, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Clinical Research Institute

Locations

Huntington Memorial Hospital

Pasadena, California, United States

Yale University School of Medicine

New Haven, Connecticut, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Brigham and Woman's Hospital

Boston, Massachusetts, United States

Mission Hospital

Asheville, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center Dallas

Dallas, Texas, United States

Countries

United States

References

Belcastro V, Vidale S, Pierguidi L, Sironi L, Tancredi L, Striano P, Taborelli A, Arnaboldi M. Intravenous lacosamide as treatment option in post-stroke non convulsive status epilepticus in the elderly: a proof-of-concept, observational study. Seizure. 2013 Dec;22(10):905-7. doi: 10.1016/j.seizure.2013.07.011. Epub 2013 Aug 13.

Reference Type: DERIVED

PMID: 23953988 (View on PubMed)

Other Identifiers

Pro00037794

Identifier Type: OTHER

Identifier Source: secondary_id

DCRI-CEMC101.01

Identifier Type: -

Identifier Source: secondary_id

Pro00033295

Identifier Type: -

Identifier Source: org_study_id