Ketamine for the Treatment of Refractory Status Epilepticus

NCT07177235 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: iRISID-2025-0404
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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).

Conditions

Refractory Status Epilepticus

Outcome Measures

Primary Outcomes (1)

• Time to seizure cessation

  Time from initiation of anesthetic infusion (midazolam or midazolam plus ketamine) to the time of last electrographic seizure

  72 hours

Study Arms (2)

Early ketamine

ACTIVE COMPARATOR

Initiation of ketamine infusion simultaneously with midazolam infusion as the third-line anesthetic treatment

Drug: Ketamine; Drug: Midazolam

Late ketamine

ACTIVE COMPARATOR

Initiation of ketamine infusion only after midazolam infusion has been started

Drug: Ketamine; Drug: Midazolam

Interventions

Ketamine DRUG

Timing of ketamine initiation will differ between groups (early versus late ketamine)

Early ketamine; Late ketamine

Midazolam DRUG

Midazolam infusion will be initiated at the same time in both groups

Early ketamine; Late ketamine

Eligibility Criteria

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

You may qualify if:

• Adults 18 years of age or older
• Patients with refractory status epilepticus unresponsive to appropriately dosed first line agents administered intravenous or intraosseous and one second line agent
• First line agents: lorazepam, midazolam, or diazepam
• Second line agents: phenytoin (20 mg/kg), valproate (40 mg/kg), levetiracetam (60 mg/kg), lacosamide (400 mg)
• All etiologies of status epilepticus will be included

You may not qualify if:

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

Sponsors & Collaborators

• Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (7)

• Bell ML, Whitehead AL, Julious SA. Guidance for using pilot studies to inform the design of intervention trials with continuous outcomes. Clin Epidemiol. 2018 Jan 18;10:153-157. doi: 10.2147/CLEP.S146397. eCollection 2018.

  PMID: 29403314 BACKGROUND

• Bruno A, Akinwuntan AE, Lin C, Close B, Davis K, Baute V, Aryal T, Brooks D, Hess DC, Switzer JA, Nichols FT. Simplified modified rankin scale questionnaire: reproducibility over the telephone and validation with quality of life. Stroke. 2011 Aug;42(8):2276-9. doi: 10.1161/STROKEAHA.111.613273. Epub 2011 Jun 16.

  PMID: 21680905 BACKGROUND

• Golub D, Yanai A, Darzi K, Papadopoulos J, Kaufman B. Potential consequences of high-dose infusion of ketamine for refractory status epilepticus: case reports and systematic literature review. Anaesth Intensive Care. 2018 Sep;46(5):516-528. doi: 10.1177/0310057X1804600514.

  PMID: 30189827 BACKGROUND

• Janssen PM, Visser NA, Dorhout Mees SM, Klijn CJ, Algra A, Rinkel GJ. Comparison of telephone and face-to-face assessment of the modified Rankin Scale. Cerebrovasc Dis. 2010 Jan;29(2):137-9. doi: 10.1159/000262309. Epub 2009 Dec 1.

  PMID: 19955737 BACKGROUND

• Legriel S, Oddo M, Brophy GM. What's new in refractory status epilepticus? Intensive Care Med. 2017 Apr;43(4):543-546. doi: 10.1007/s00134-016-4501-6. Epub 2016 Aug 20. No abstract available.

  PMID: 27544138 BACKGROUND

• Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, Shorvon S, Lowenstein DH. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015 Oct;56(10):1515-23. doi: 10.1111/epi.13121. Epub 2015 Sep 4.

  PMID: 26336950 BACKGROUND

• Fletman EW, Cleymaet S, Salvatore A, Devlin K, Pickard A, Shah SO. Ketamine plus midazolam compared to midazolam infusion for the management of refractory status epilepticus. Clin Neurol Neurosurg. 2024 Nov;246:108592. doi: 10.1016/j.clineuro.2024.108592. Epub 2024 Oct 12.

  PMID: 39418930 BACKGROUND

MeSH Terms

Conditions

Status Epilepticus

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Syed O Shah, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elizabeth Fletman, DO

CONTACT

215-955-7000; elizabeth.fletman@jefferson.edu

Syed 0 Shah, MD

CONTACT

Syed.Shah@Jefferson.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Neurology and Neurological Surgery

Study Record Dates

• First Submitted: September 3, 2025
• First Posted: September 16, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: September 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)