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Refractory Status EpilepticusPhase 4NCT07177235

Ketamine for the Treatment of Refractory Status Epilepticus

A Phase 4 study testing Ketamine and Midazolam in people with Refractory Status Epilepticus, run by Thomas Jefferson University at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Refractory Status Epilepticus
What is being tested?
Ketamine and Midazolam
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
Nov 2025to Jul 2028
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Elizabeth Fletman, DO contact

215-955-7000

elizabeth.fletman@jefferson.edu

Syed 0 Shah, MD contact

Syed.Shah@Jefferson.edu

United States1 site

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: Early Ketamine Plus Midazolam Versus Ketamine Plus Midazolam for the Treatment of Refractory Status Epilepticus

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).

Read the 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.

Being tested
Ketamine, Midazolam
Medical subject headings
Status Epilepticus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KetamineDrug

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

  • MidazolamDrug

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

Study groups in NCT07177235
Study groupRoleWhat they receive
Early ketamineActive comparatorInitiation of ketamine infusion simultaneously with midazolam infusion as the third-line anesthetic treatment
Receives: Drug: Ketamine; Drug: Midazolam
Late ketamineActive comparatorInitiation of ketamine infusion only after midazolam infusion has been started
Receives: Drug: Ketamine; Drug: Midazolam

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to seizure cessation

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

    Measured: 72 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Sep 2025
  2. Study startNov 2025 (estimated)
  3. Primary completionJul 2027 (estimated)
  4. Study completionJul 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07177235
Sponsor's protocol ID
iRISID-2025-0404
Status last verified
Sep 2025
First submitted
3 Sep 2025
Last updated
16 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 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.

    PubMed 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.

    PubMed 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.

    PubMed 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.

    PubMed 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.

    PubMed 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.

    PubMed 39418930

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ketamine and Midazolam in people with Refractory Status Epilepticus, run by Thomas Jefferson University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 16 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Elizabeth Fletman, DO (215-955-7000, elizabeth.fletman@jefferson.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to seizure cessation (time frame: 72 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07177235, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2025.

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