Treatment of Refractory Status Epilepticus

Overview

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.

Full Title of Study: “A Randomized Clinical Trial for the Treatment of Refractory Status Epilepticus”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: None (Open Label)
• Study Primary Completion Date: March 2010

Detailed Description

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.

Interventions

• Drug: propofol
  • liquid, mg/kg.h, titrated after EEG
• Drug: thiopental/pentobarbital
  • liquid, mg/kg.h, titrated after EEG

Arms, Groups and Cohorts

• Active Comparator: 1
  • propofol, 2mg/kg as bolus, then titrated up to EEG burst-suppression as a continuous infusion; no maximum doses defined
• Active Comparator: 2
  • thiopental/pentobarbital, 2mg/kg as bolus, then titrated up to EEG burst-suppression as a continuous infusion; no maximum doses defined

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 16 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Brigham and Women’s Hospital
• Provider of Information About this Clinical Study
  • Principal Investigator: Andrea O. Rossetti, MD, Dr – Brigham and Women’s Hospital
• Overall Official(s)
  • Andrea O. Rossetti, MD, Principal Investigator, BrighamHospital/CHUV

Citations Reporting on Results

Rossetti AO, Milligan TA, Vulliémoz S, Michaelides C, Bertschi M, Lee JW. A randomized trial for the treatment of refractory status epilepticus. Neurocrit Care. 2011 Feb;14(1):4-10. doi: 10.1007/s12028-010-9445-z.