Ketamine for the Treatment of Refractory Status Epilepticus
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Ketamine, Midazolam.
- Who it may be relevant to
- Registry conditions: Refractory Status Epilepticus. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Early Ketamine Plus Midazolam Versus Ketamine Plus Midazolam for the Treatment of Refractory Status Epilepticus
Overview
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.
Interventions
- Drug Ketamine
Timing of ketamine initiation will differ between groups (early versus late ketamine) - Drug Midazolam
Midazolam infusion will be initiated at the same time in both groups
Primary outcome measures
- Time to seizure cessation [Time frame: 72 hours]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- 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)
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 1 center
- Thomas Jefferson University Hospital — Philadelphia
Publications
- 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
- 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
- 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
- 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
- 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
- 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
- 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
Identifiers
NCT: NCT07177235 · iRISID-2025-0404