Treatment of Refractory Status Epilepticus

Study Overview
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Brief Summary
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The purpose of this study is to determine whether propofol or barbiturates should be preferred in the treatment of status epilepticus (continuous seizure activity) refractory to 2 standard antiepileptic agents.

Detailed Description
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Refractory status epilepticus (SE) develops in 31%-44% of patients with SE, with a mortality of 16%-23%. Coma induction is advocated for its management. Propofol and barbiturates are the most used agents, but no comparative study has been performed. In consideration of the uncertainty regarding the relative effectiveness, despite several retrospective data, a prospective investigation is needed. The objective is to assess the effectiveness (SE control, adverse events) of a first course of propofol versus barbiturates in the treatment of refractory SE, in adults with refractory SE not due to cerebral anoxia. Comparison: Coma induction with standardized doses of propofol or barbiturates titrated towards burst-suppression on EEG, then assessment of the proportion of patients achieving a control of SE.

Official Title
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A Randomized Clinical Trial for the Treatment of Refractory Status Epilepticus

Conditions
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Status Epilepticus

Intervention / Treatment
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* Drug: propofol
* Drug: thiopental/pentobarbital


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with refractory status epilepticus not due to cerebral anoxia, needing coma induction for clinical management. Exclusion Criteria: Age < 16 years old. Known pregnancy. Cerebral anoxia as SE etiology. Epilepsia partialis continua (simple partial SE). Known intolerance to the study drugs. Known mitochondrial disorder, hyperlipidemia, or significant rhabdomyolysis.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>propofol, 2mg/kg as bolus, then titrated up to EEG burst-suppression as a continuous infusion; no maximum doses defined | Drug: propofol<br>* liquid, mg/kg.h, titrated after EEG<br>* Other names: Disoprivan;|
| Active Comparator: 2<br>thiopental/pentobarbital, 2mg/kg as bolus, then titrated up to EEG burst-suppression as a continuous infusion; no maximum doses defined | Drug: thiopental/pentobarbital<br>* liquid, mg/kg.h, titrated after EEG<br>* Other names: Pentotal /Thiopentone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Refractory Status Epilepticus Controlled With First Course of Study Drug | Control of status epilepticus refractory to benzodiazepines and a first antiepileptic drug after administration of the study drug; dichotomous assessment (yes/no) | after return of continuous EEG activity (typically after 36 hours - 5 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Outcome at Day 21 | Return to baseline clinical conditions (i.e.: no new handicap, no death) | 21 days | 
| Patients With Infectious Complications Requiring Specific Treatment |  | 10 days | 
| Patients With Hypotension Requiring Specific Treatment |  | 10 days | 
| Patients With Propofol Infusion Syndrome | Propofol infusion syndrome (PRIS) is a severe metabolic alteration with elevation of lactate, CK, and triglycerides. | 10 days | 
| Intubation Time in Survivors |  | Up to 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Refractory status epilepticus,, coma-induction,, treatment,, propofol,, barbiturates,, efficacy,, safety.