Ketamine for the Treatment of Refractory Status Epilepticus

Not Applicable

Not yet recruiting

• Conditions: Refractory Status Epilepticus
• Interventions: Drug: Ketamine; Drug: Midazolam

• Registration Number: NCT07177235
• Lead Sponsor: Thomas Jefferson University

Brief Summary

This pilot feasibility study aims to examine how the timing of ketamine introduction as a third-line anti-seizure medication infusion relates to seizure cessation in patients with refractory status epilepticus (RSE).

Detailed Description

Patients admitted to the Jefferson Neurological Intensive Care Unit with seizures or status epilepticus will be screened for eligibility. Surrogate consent will be obtained from the participants legally authorized representative (LAR) by study personnel for eligible patients using remote e-consent process via RedCap. Participants will be randomized 1:1 to receive either early intravenous ketamine plus midazolam infusion or the current institutional protocol of midazolam followed by late ketamine infusion (Fernandez et al., 2018). Continuous video EEG monitoring will guide medication titration, increasing doses every 20 minutes for ongoing seizure activity. The primary goal of this study is to examine the feasibility of the protocol and obtain estimates of the timing of seizure cessation. The primary outcome is time to seizure cessation, defined as the time from initiation of anesthetic infusion (midazolam or midazolam plus ketamine) to the time of last electrographic seizure. The investigators will also collect preliminary data on other clinical measures that would serve as secondary outcomes for future trials. These clinical measures include progression to super refractory status epilepticus, intensive care unit and hospital length of stay, duration of mechanical ventilation, and functional outcomes assessed by the modified Rankin Scale at discharge, 3 months, and 6 months. This study does not evaluate ketamine as a novel therapy but rather assesses a minor modification in the timing of ketamine administration to optimize seizure control.

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-03
• Study First Submitted QC: 2025-09-09
• Last Update Submitted: 2025-09-09
• Study First Posted: 2025-09-16
• Last Update Posted: 2025-09-16
• Study Start: 2025-11-01
• Primary Completion: 2027-07
• Study Completion: 2028-07-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Adults 18 years of age or older

2. Patients with refractory status epilepticus unresponsive to appropriately dosed first line agents administered intravenous or intraosseous and one second line agent

   1. First line agents: lorazepam, midazolam, or diazepam
   2. Second line agents: phenytoin (20 mg/kg), valproate (40 mg/kg), levetiracetam (60 mg/kg), lacosamide (400 mg)

3. All etiologies of status epilepticus will be included

Exclusion Criteria

1. Exclusively psychogenic non epileptic seizures
2. Pregnant individuals
3. Incarcerated individuals
4. Patients with hypersensitivity to ketamine or any component of the formulation
5. Conditions in which an increase in blood pressure would be hazardous
6. Focal motor status epilepticus
7. Status epilepticus lasting > 24 hours prior to enrollment (SRSE)
8. Patients with EEG in the ictal-interictal continuum (IIC)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early ketamine	Ketamine	Initiation of ketamine infusion simultaneously with midazolam infusion as the third-line anesthetic treatment
Early ketamine	Midazolam	Initiation of ketamine infusion simultaneously with midazolam infusion as the third-line anesthetic treatment
Late ketamine	Ketamine	Initiation of ketamine infusion only after midazolam infusion has been started
Late ketamine	Midazolam	Initiation of ketamine infusion only after midazolam infusion has been started

Primary Outcome Measures

Name	Time	Method
Time to seizure cessation	72 hours	Time from initiation of anesthetic infusion (midazolam or midazolam plus ketamine) to the time of last electrographic seizure

Trial Locations

Locations (1)

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States