Intravenous Lacosamide Compared With Fosphenytoin in the Treatment of Patients With Frequent Nonconvulsive Seizures
Condition: Nonconvulsive Seizures
MeSH terms: Seizures
Intervention: fPHT; LCM
Intervention description: 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.; 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 MeSH terms: Lacosamide; Fosphenytoin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Investigator)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Nonconvulsive Seizures

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.
    

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.