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

Primary Purpose

Epilepsy, Status Epilepticus

Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
levetiracetam
lacosamide
Ketamine
Phenobarbital
Sponsored by
Mid-Atlantic Epilepsy and Sleep Center, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring refractory status epilepticus, levetiracetam, lacosamide, ketamine

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

  • MidAtlantic Epilepsy and Sleep Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

levetiracetam

lacosamide

ketamine

phenobarbital

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Cessation of status epilepticus by EEG.
The cessation of ictal epileptic EEG activity measured by EEG.

Secondary Outcome Measures

Cessation of status epilepticus by clinical examination
Measurement of the time to status epilepticus cessation by clinical examination.

Full Information

First Posted
December 12, 2014
Last Updated
August 28, 2017
Sponsor
Mid-Atlantic Epilepsy and Sleep Center, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02726867
Brief Title
Levetiracetam, Lacosamide and Ketamine as Adjunctive Treatment of Refractory Status Epilepticus
Official Title
Evaluation of Efficacy and Safety of Levetiracetam, Lacosamide and Ketamine as Adjunctive Treatment of Refractory Status Epilepticus
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Withdrawn
Why Stopped
No participants enrolled
Study Start Date
February 2014 (undefined)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mid-Atlantic Epilepsy and Sleep Center, LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

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)
Detailed Description
40 18-70 year old men and women with refractory status epilepticus, defined as status epilepticus continuing for >1 hour after completion of standard treatment with lorazepam (or midazolam) and i.v. phenytoin (or fos-phenytoin),will be enrolled. Participants will be randomized into four treatment arms, levetiracetam 4000 (Group A, n=10), lacosamide 600 mg (Group B, n=10), ketamine 2.5 mg/kg (group C,n=10),and phenobarbital 15 mg/kg (Group D, n=10) in a 1:1:1:1 ratio. Baseline evaluations will include continuous EEG, phenytoin levels prior to study intervention, CBC, CMP, serum Ca, Po4 and Mg. Treatment will consist of levetiracetam 4000 mg i.v. over 10 minutes, lacosamide 600 mg i.v. over 10 minutes, ketamine 2.5 mg/kg over 10 minutes, or phenobarbital 15 mg/kg mg i.v. at 100 mg/minute rate. Participants will be evaluated with ongoing physical examination and continuous EEG monitoring. Continuous EEG monitoring will be started before initiation of the study treatment, with documentation of electrographic status epilepticus. It will continue throughout the treatment period. Subjects will be observed for 1 hour clinically and with continuous EEG monitoring for cessation of SE. Participants in whom status epilepticus stops within 60 minutes of completion of study treatment will continue to receive phenytoin (150 mg i.v. q 12 hours, standard dose) and the study medication (levetiracetam 1500 mg i.v. q 12 hourly, lacosamide 300 mg q 12 hourly, ketamine 50 mg qid (vs. 40 mcg/kg/min i.v. infusion, as clinically applicable, or phenobarbital 90 mg i.v. q 12 hourly). Continuous EEG monitoring will continue for 72 hours to monitor for relapse of status epilepticus. Participants in whom status epilepticus fails to stop within 60 minutes after completion of study treatment ("non-responders") will undergo standard treatment with medically-induced coma, with intubation/ventilation and i.v. midazolam or propofol treatment at a dose to be titrated to EEG effect of "burst suppression" or suppression of all background activity. All patients, responders and non-responders alike, will continue treatment with phenytoin i.v., 150 mg q 12 hourly or, for conscious patients, 300 mg p.o. qhs for 72 hours after completion of study treatment. In patients requiring medical coma after study treatments (non-responders), medical coma will be discontinued after 48 hours. All participants will continue to be monitored with continuous EEG for 72 hours from completion of study treatment. If status epilepticus returns during this time, medical coma will be re-instituted and patients will be treated according to standard clinical care for prolonged SE

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy, Status Epilepticus
Keywords
refractory status epilepticus, levetiracetam, lacosamide, ketamine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
levetiracetam
Arm Type
Active Comparator
Arm Description
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.
Arm Title
lacosamide
Arm Type
Active Comparator
Arm Description
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.
Arm Title
ketamine
Arm Type
Active Comparator
Arm Description
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.
Arm Title
phenobarbital
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
levetiracetam
Other Intervention Name(s)
Keppra
Intervention Description
Treatment will consist of LEV 4000 mg i.v. over 10 minutes.
Intervention Type
Drug
Intervention Name(s)
lacosamide
Other Intervention Name(s)
Vimpat
Intervention Description
Treatment will consist of LCM 600 mg i.v. over 10 minutes
Intervention Type
Drug
Intervention Name(s)
Ketamine
Other Intervention Name(s)
Ketalar
Intervention Description
Treatment will consist of KET 2.5 mg/kg over 10 minutes
Intervention Type
Drug
Intervention Name(s)
Phenobarbital
Other Intervention Name(s)
Phenobarb
Intervention Description
Treatment will consist of PHB 15 mg/kg mg i.v. at 100 mg/minute rate
Primary Outcome Measure Information:
Title
Cessation of status epilepticus by EEG.
Description
The cessation of ictal epileptic EEG activity measured by EEG.
Time Frame
60 minutes
Secondary Outcome Measure Information:
Title
Cessation of status epilepticus by clinical examination
Description
Measurement of the time to status epilepticus cessation by clinical examination.
Time Frame
60 minutes
Other Pre-specified Outcome Measures:
Title
Recurrence of status epilepticus.
Description
The recurrence of status epilepticus in responders in during the 72 hours of monitoring.
Time Frame
72 hours
Title
Rate of early treatment discontinuation
Description
Rate of treatment discontinuation within 72 hours.
Time Frame
72 hours
Title
Duration of hospitalization
Description
Investigators will count the number days of hospitalization.
Time Frame
3 months
Title
Number of participants with neurological deficit.
Description
Investigators will identify the number of patients with neurological deficit at 3 months are the other measure outcomes.
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18-70 Ability and willingness by surrogates to signed informed consent form. Clinically and electrographically documented ongoing SE lasting ≥1 hour- ≤24 hours Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pavel Klein, M.D.
Organizational Affiliation
Mid-Atlantic Epilepsy and Sleep Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
MidAtlantic Epilepsy and Sleep Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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