Levetiracetam, Lacosamide and Ketamine as Adjunctive Treatment of Refractory Status Epilepticus

NCT02726867 | Withdrawn Phase 3

• 1 other identifier: MAES-003
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the efficacy and safety of levetiracetam , lacosamide and ketamine treatment of refractory status epilepticus. This will be a randomized, open-label, four-arm pilot study comparing time to cessation of refractory status epilepticus, determined by continuous EEG monitoring, in patients with refractory status epilepticus. Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical status epilepticus for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) either 4000 mg levetiracetam, 600 mg lacosamide (Group B), 2.5 mg/kg ketamine or phenobarbital 15 mg/kg phenobarbital (Group D)

Conditions

Epilepsy; Status Epilepticus

Keywords

refractory status epilepticus; levetiracetam; lacosamide; ketamine

Outcome Measures

Primary Outcomes (1)

• Cessation of status epilepticus by EEG.

  The cessation of ictal epileptic EEG activity measured by EEG.

  60 minutes

Secondary Outcomes (1)

• Cessation of status epilepticus by clinical examination

  60 minutes

Other Outcomes (4)

• Recurrence of status epilepticus.

  72 hours

• Rate of early treatment discontinuation

  72 hours

• Duration of hospitalization

  3 months

Study Arms (4)

levetiracetam

ACTIVE COMPARATOR

Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) 4000 mg levetiracetam.

Drug: levetiracetam

lacosamide

ACTIVE COMPARATOR

Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) 600 mg lacosamide.

Drug: lacosamide

ketamine

ACTIVE COMPARATOR

Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) 2.5 mg/kg ketamine.

Drug: Ketamine

phenobarbital

ACTIVE COMPARATOR

Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin (PHT) with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after PHT loading will receive intravenously (i.v.) phenobarbital 15 mg/kg.

Drug: Phenobarbital

Interventions

levetiracetam DRUG

Treatment will consist of LEV 4000 mg i.v. over 10 minutes.

Also known as: Keppra

levetiracetam

lacosamide DRUG

Treatment will consist of LCM 600 mg i.v. over 10 minutes

Also known as: Vimpat

lacosamide

Ketamine DRUG

Treatment will consist of KET 2.5 mg/kg over 10 minutes

Also known as: Ketalar

ketamine

Phenobarbital DRUG

Treatment will consist of PHB 15 mg/kg mg i.v. at 100 mg/minute rate

Also known as: Phenobarb

phenobarbital

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70
• Ability and willingness by surrogates to signed informed consent form.
• Clinically and electrographically documented ongoing SE lasting ≥1 hour- ≤24 hours

You may not qualify if:

• Creatinine \> 2.5 mg/dl
• Any systemic illness or unstable medical condition that might pose additional risk, including: cardiac, metabolic or endocrine disturbances, renal or liver disease
• Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements
• Pregnancy
• Inability or unwillingness of subject or legal surrogate to give written informed consent
• Known allergy to a study drug
• Hypo- or hyperglycemia as cause of SE

Sponsors & Collaborators

• Mid-Atlantic Epilepsy and Sleep Center, LLC: lead

Study Sites (1)

MidAtlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

MeSH Terms

Conditions

Epilepsy; Status Epilepticus

Interventions

Levetiracetam; Lacosamide; Ketamine; Phenobarbital

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Seizures; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Barbiturates; Pyrimidinones; Pyrimidines

Study Officials

• Pavel Klein, M.D.

  Mid-Atlantic Epilepsy and Sleep Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: December 12, 2014
• First Posted: April 4, 2016
• Study Start: February 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: August 29, 2017

Record last verified: 2017-08

Locations

US (1)