Ketamine add-on Therapy for Established Status Epilepticus Treatment Trial (KESETT) (KESETT)

May 12, 2026 updated by: Jaideep Kapur, MD, University of Virginia
The goal of this clinical trial is to determine if treatment of patients with two doses of ketamine plus levetiracetam versus levetiracetam alone leads to more effective control of status epilepticus.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

KESETT is a multicenter, randomized, blinded study to determine whether adding 1 mg/kg or 3 mg/kg dose of KET to 60 mg/kg LEV can terminate status epilepticus (SE) in a larger fraction of subjects with benzodiazepine-refractory SE than those treated with LEV (60 mg/kg) alone.

The primary outcome is termination of SE from 15 minutes after starting the study drug infusion, sustained until 60 minutes from enrollment without using additional anti-seizure medication. Termination of SE is determined by (1) improving consciousness and absence of clinically apparent seizures at 60 minutes or (2) absence of any electrographic SE after 15 minutes in those with EEG monitoring and no improvement in consciousness.

Secondary objectives include determining the relative safety of the treatment arms on defined safety outcomes and all adverse events, analysis of secondary/exploratory efficacy outcomes, and evaluation of both effectiveness and safety in the pediatric subpopulation.

The trial will initially allocate subjects equally (1:1:1) for the first 350 participants (burn-in period) before transitioning to response-adaptive randomization. Interim analyses will be conducted for efficacy and futility beginning when 350 subjects have been randomized, and will occur every 100 subjects thereafter. A maximum of 770 participants will be enrolled.

Study Type

Interventional

Enrollment (Estimated)

770

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • Recruiting
        • Banner University Medical Center - Tucson Campus
        • Contact:
        • Principal Investigator:
          • Aaron Leetch, MD
    • California
      • Los Angeles, California, United States, 90027
        • Not yet recruiting
        • Children's Hospital Los Angeles
        • Contact:
        • Principal Investigator:
          • Ara Festekjian, MD
      • Los Angeles, California, United States, 90024
        • Not yet recruiting
        • Ronald Reagan UCLA Medical Center
        • Contact:
        • Principal Investigator:
          • Richelle Cooper, MD
      • Palo Alto, California, United States, 94304
        • Not yet recruiting
        • Stanford University Medical Center
        • Contact:
        • Principal Investigator:
          • Alexandra June Gordon, MD
      • Sacramento, California, United States, 95817
        • Recruiting
        • UC Davis Medical Center
        • Principal Investigator:
          • Daniel Nishijima, MD
        • Contact:
      • San Francisco, California, United States, 94143
        • Not yet recruiting
        • UCSF Medical Center
        • Contact:
        • Principal Investigator:
          • Debbie Madhok, MD
      • San Francisco, California, United States, 94143
        • Not yet recruiting
        • San Francisco General Hospital
        • Contact:
        • Principal Investigator:
          • Debbie Madhok, MD
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Recruiting
        • Yale New Haven Hospital
        • Contact:
        • Principal Investigator:
          • Charles Wira, MD
    • Delaware
      • Newark, Delaware, United States, 19718
        • Not yet recruiting
        • Christiana Hospital
        • Principal Investigator:
          • Jason Nomura, MD
        • Contact:
      • Wilmington, Delaware, United States, 19803
        • Not yet recruiting
        • Nemours Children's Hospital
        • Contact:
        • Principal Investigator:
          • Amy Thompson, MD
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Recruiting
        • Children's National Medical Center
        • Principal Investigator:
          • James Chamberlain, MD
        • Contact:
    • Florida
      • Orlando, Florida, United States, 32806
        • Not yet recruiting
        • Orlando Regional Medical Center
        • Contact:
        • Principal Investigator:
          • Dipali Nemade, MD
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Recruiting
        • Grady Memorial Hospital
        • Contact:
        • Principal Investigator:
          • Jonathan Ratcliff, MD, MPH
      • Atlanta, Georgia, United States, 30329
        • Recruiting
        • Arthur M. Blank Hospital
        • Principal Investigator:
          • Claudia Morris, MD
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Not yet recruiting
        • University Of Chicago Medical Center
        • Contact:
        • Principal Investigator:
          • David Beiser, MD
      • Chicago, Illinois, United States, 60611
        • Not yet recruiting
        • Northwestern Memorial Hospital
        • Contact:
        • Principal Investigator:
          • Peter Pruitt, MD
      • Chicago, Illinois, United States, 60637
        • Not yet recruiting
        • Comer Children's Hospital
        • Contact:
        • Principal Investigator:
          • David Beiser, MD
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Not yet recruiting
        • Riley Hospital for Children
        • Contact:
          • Benjamin Nti, MD
          • Phone Number: 317-416-7997
          • Email: bnti@iu.edu
        • Principal Investigator:
          • Benjamin Nti, MD
      • Indianapolis, Indiana, United States, 46202
        • Not yet recruiting
        • IU Health Methodist Hospital
        • Contact:
          • Daniel Udrea, MD
          • Phone Number: 317-274-0829
          • Email: dudrea@iu.edu
        • Principal Investigator:
          • Daniel Udrea, MD
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Not yet recruiting
        • University of Iowa Medical Center
        • Contact:
        • Principal Investigator:
          • Brett Faine, MD
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Not yet recruiting
        • University of Maryland Medical Center
        • Contact:
        • Principal Investigator:
          • Jennifer Hopp, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Not yet recruiting
        • Massachusetts General Hospital
        • Contact:
        • Principal Investigator:
          • Michael Filbin, MD
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan University Hospital
        • Contact:
        • Principal Investigator:
          • Mariama Runcie, MD
      • Detroit, Michigan, United States, 48202
        • Not yet recruiting
        • Henry Ford Hospital
        • Principal Investigator:
          • Joseph Miller, MD
        • Contact:
      • Detroit, Michigan, United States, 48201
        • Not yet recruiting
        • Detroit Receiving Hospital
        • Contact:
        • Principal Investigator:
          • Wazim Mohamed, MD
      • Detroit, Michigan, United States, 48201
        • Not yet recruiting
        • Sinai-Grace Hospital
        • Contact:
        • Principal Investigator:
          • Arun Sherma, MD
    • Minnesota
      • Minneapolis, Minnesota, United States, 55415
        • Not yet recruiting
        • Hennepin County Medical Center
        • Principal Investigator:
          • Brian Driver, MD
        • Contact:
      • Minneapolis, Minnesota, United States, 55455
        • Not yet recruiting
        • University of Minnesota Medical Center
        • Contact:
        • Principal Investigator:
          • James Miner, MD
      • Minneapolis, Minnesota, United States, 55414
        • Not yet recruiting
        • University of Minnesota Masonic Children's Hospital
        • Contact:
        • Principal Investigator:
          • James Miner, MD
    • New York
      • Syracuse, New York, United States, 13210
        • Not yet recruiting
        • SUNY Upstate Medical University
        • Contact:
        • Principal Investigator:
          • Lindsay Nausin, DO
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Not yet recruiting
        • Duke University Hospital
        • Contact:
        • Principal Investigator:
          • Alexander Limkakeng, MD
      • Durham, North Carolina, United States, 27710
        • Not yet recruiting
        • Duke Regional Hospital
        • Contact:
        • Principal Investigator:
          • Alexander Limkakeng, MD
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • Not yet recruiting
        • University of Cincinnati Medical Center
        • Contact:
        • Principal Investigator:
          • Jason McMullan, MD
      • Columbus, Ohio, United States, 43205
        • Recruiting
        • Nationwide Children's Hospital
        • Contact:
        • Principal Investigator:
          • Aarti Gaglani, MD
      • Columbus, Ohio, United States, 43210
        • Not yet recruiting
        • OSU Wexner Medical Center
        • Contact:
        • Principal Investigator:
          • Kirstin Acus, MD
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health & Science University Hospital
        • Contact:
          • Bory Kea, MD
          • Phone Number: 503-494-8083
          • Email: kea@ohsu.edu
        • Principal Investigator:
          • Bory Kea, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Recruiting
        • Temple University Hospital
        • Contact:
        • Principal Investigator:
          • Derek Isenberg, MD
      • Philadelphia, Pennsylvania, United States, 19104
        • Not yet recruiting
        • Hospital of the University of Pennsylvania
        • Contact:
        • Principal Investigator:
          • John Greenwood, MD
      • Philadelphia, Pennsylvania, United States, 19104
        • Not yet recruiting
        • Penn Presbyterian Medical Center
        • Contact:
        • Principal Investigator:
          • John Greenwood, MD
      • Philadelphia, Pennsylvania, United States, 19141
        • Not yet recruiting
        • Jefferson Einstein Philadelphia Hospital
        • Contact:
        • Principal Investigator:
          • Joseph Herres, DO
      • Pittsburgh, Pennsylvania, United States, 15224
        • Recruiting
        • UPMC Children's Hospital of Pittsburgh
        • Contact:
        • Principal Investigator:
          • Robert Hickey, MD
      • Pittsburgh, Pennsylvania, United States, 15213
        • Not yet recruiting
        • UPMC Presbyterian Hospital
        • Contact:
        • Principal Investigator:
          • Adam Frisch, MD
      • West Reading, Pennsylvania, United States, 19611
        • Recruiting
        • Reading Hospital
        • Contact:
        • Principal Investigator:
          • Adam Sigal, MD
    • Texas
      • Dallas, Texas, United States, 75235
        • Not yet recruiting
        • Children's Medical Center Dallas
        • Contact:
        • Principal Investigator:
          • Pamela Okada, MD
      • Houston, Texas, United States, 77030
        • Recruiting
        • Memorial Hermann Texas Medical Center
        • Contact:
        • Principal Investigator:
          • Kayleigh Fischer, MD
    • Utah
      • Salt Lake City, Utah, United States, 84108
        • Not yet recruiting
        • Primary Children's Hospital
        • Contact:
        • Principal Investigator:
          • Maija Holsti, MD, MPH
      • Salt Lake City, Utah, United States, 84112
        • Not yet recruiting
        • University of Utah Healthcare
        • Contact:
        • Principal Investigator:
          • Scott Youngquist, MD
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia Medical Center
        • Principal Investigator:
          • Thomas Hartka, MD
        • Contact:
      • Richmond, Virginia, United States, 23298
        • Not yet recruiting
        • VCU Medical Center
        • Contact:
        • Principal Investigator:
          • Lisa Merck, MD, MPH, MHA
    • Washington
      • Seattle, Washington, United States, 98104
        • Recruiting
        • Harborview Medical Center
        • Contact:
        • Principal Investigator:
          • Vasisht Srinivasan, MD
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Not yet recruiting
        • Froedtert Hospital
        • Contact:
        • Principal Investigator:
          • Jamie Jasti, MD
      • Milwaukee, Wisconsin, United States, 53226
        • Not yet recruiting
        • Children's Hospital of Wisconsin
        • Contact:
        • Principal Investigator:
          • Keli Coleman, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • The patient was witnessed to have a convulsive seizure for greater than 5-minute duration
  • The patient received an adequate dose of benzodiazepines. The doses may be divided.
  • The last dose of a benzodiazepine was administered 5-30 minutes before study drug administration.
  • Continued or recurring seizures in the Emergency Department.
  • Age 1 years or older
  • Known or estimated weight ≥10 Kg

Exclusion Criteria:

  • Known pregnancy
  • Prisoner
  • Opt-out identification or otherwise known to be previously enrolled in KESETT
  • Treatment with a second line anticonvulsant (FOS, PHT, VPA, LEV, phenobarbital, or other agents defined in the MoP) for this episode of SE
  • Treatment with sedatives with anticonvulsant properties other than benzodiazepines for this episode of SE(propofol, etomidate, ketamine or other agents defined in the MoP)
  • Endotracheal intubation prior to enrollment
  • Acute traumatic brain injury clearly precedes seizures
  • Scalp injury or burn preventing EEG placement
  • Known allergy or other known contraindication to KET or LEV
  • Hypoglycemia < 50 mg/dL
  • Hyperglycemia > 400 mg/dL
  • Cardiac arrest / post-anoxic seizures

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Levetiracetam
Levetiracetam (LEV) (60 mg/Kg)
Drug: Levetiracetam (LEV) (60 mg/Kg)

The study drug will be produced at the central pharmacy, a GMP facility at the University of California, Davis. Diluted formulations are expected to remain stable for months when stored at room temperature. Expiration dates for study drugs will be determined and adjusted based on ongoing stability testing performed on study drugs prepared at the GMP facility for the study.

All three formulations will be transparent solutions. None of the formulations are reported to consistently cause adverse effects at the infusion site. The method of drug administration, including volume and rate of infusion, is identical for all three drugs. These factors ensure that drug administration will be blinded.
Experimental: Levetiracetam + low dose Ketamine
LEV 60 mg/mL + 1 mg/mL KET
Drug: Levetiracetam (LEV) (60 mg/Kg) + 1 mg/kg Ketamine (KET)

The study drug will be produced at the central pharmacy, a GMP facility at the University of California, Davis. Diluted formulations are expected to remain stable for months when stored at room temperature. Expiration dates for study drugs will be determined and adjusted based on ongoing stability testing performed on study drugs prepared at the GMP facility for the study.

All three formulations will be transparent solutions. None of the formulations are reported to consistently cause adverse effects at the infusion site. The method of drug administration, including volume and rate of infusion, is identical for all three drugs. These factors ensure that drug administration will be blinded.
Experimental: Levetiracetam + high dose Ketamine
LEV 60 mg/mL + 3 mg/mL KET increasing up to a weight of 75 kg
Drug: Levetiracetam (LEV) (60 mg/Kg) + 3 mg/kg Ketamine (KET)

The study drug will be produced at the central pharmacy, a GMP facility at the University of California, Davis. Diluted formulations are expected to remain stable for months when stored at room temperature. Expiration dates for study drugs will be determined and adjusted based on ongoing stability testing performed on study drugs prepared at the GMP facility for the study.

All three formulations will be transparent solutions. None of the formulations are reported to consistently cause adverse effects at the infusion site. The method of drug administration, including volume and rate of infusion, is identical for all three drugs. These factors ensure that drug administration will be blinded.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Termination of SE
Time Frame: From 15 minutes after starting the study drug infusion, sustained for 60 minutes without using additional anti-seizure medication.

Termination of SE from 15 minutes after starting the study drug infusion, sustained for 60 minutes without using additional anti-seizure medication.

Termination of SE is determined by (1) improving consciousness and absence of clinically apparent seizures at 60 minutes or (2) absence of any electrographic status epilepticus (ESE) after 15 minutes in those with EEG monitoring and no improvement in consciousness.
From 15 minutes after starting the study drug infusion, sustained for 60 minutes without using additional anti-seizure medication.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Desirability of response (DOOR) outcome
Time Frame: 60 minutes after starting the study drug infusion

One secondary outcome will be a desirability of response (DOOR) outcome which is a composite efficacy measure evaluated on a graded scale from 1 to 5 at 60 minutes, as follows:

  • No clinically evident or electrographic seizures after 15 minutes, no rescue drugs, and improving mental status by 60 minutes
  • No clinically evident or electrographic seizures after 15 minutes, not intubated, but not improving mental status at 60 minutes
  • No clinically evident or electrographic seizures after 15 minutes, but intubated or use of additional seizures medications (including medications used for intubation)
  • Any clinically evident seizure or electrographic seizure requiring rescue medicine within the timeframe between 15 and 60 minutes
  • Life-threatening hypotension or cardiac arrhythmia or death within 60 minutes

The Central Adjudication Core will determine the DOOR grade (1-5) based on clinical outcome data provided by the site and EEG data provided by the Central EEG Core.
60 minutes after starting the study drug infusion
Endotracheal intubation
Time Frame: Within 60 minutes after start of the study drug infusion
Endotracheal intubation within 60 minutes of randomization (start of study drug infusion) and duration
Within 60 minutes after start of the study drug infusion
ICU duration
Time Frame: Up to 30 days after enrollment
ICU duration during the study period for those that are admitted to the ICU as abstracted from the hospital admission record
Up to 30 days after enrollment
Hospital length-of-stay (LOS)
Time Frame: Up to 30 days after enrollment
Hospital length-of-stay (LOS) from the ED as abstracted from the hospital admission record
Up to 30 days after enrollment
Late recurrent seizure
Time Frame: Between 60 minutes and 4 hours after the start of the study drug infusion
Number of participants with late recurrent seizure between 60 minutes and 4 hours after the start of the study drug infusion
Between 60 minutes and 4 hours after the start of the study drug infusion
Time to termination of seizures
Time Frame: From the start of infusion of study drug to the cessation of electrographic seizure assessed up to 60 minutes from study drug initiation
The interval from the start of infusion of study drug to the cessation of electrographic seizure in those who meet the primary outcome
From the start of infusion of study drug to the cessation of electrographic seizure assessed up to 60 minutes from study drug initiation
Late seizures after requiring an anesthetic
Time Frame: Between 60 minutes and 24 hours after start of study drug infusion
Number of participants with late seizures after requiring an anesthetic between 60 minutes and 24 hours after start of study drug infusion
Between 60 minutes and 24 hours after start of study drug infusion
All cause mortality
Time Frame: From the start of study drug infusion to hospital discharge or day 30
All cause mortality to end of study
From the start of study drug infusion to hospital discharge or day 30

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Virginia

Collaborators

Medical University of South Carolina
Massachusetts General Hospital
University of Michigan
Children's National Research Institute

Investigators

  • Principal Investigator: Jaideep Kapur, MD, PhD, University of Virginia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 6, 2026

Primary Completion (Estimated)

June 1, 2029

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

March 24, 2025

First Submitted That Met QC Criteria

March 31, 2025

First Posted (Actual)

April 2, 2025

Study Record Updates

Last Update Posted (Actual)

May 14, 2026

Last Update Submitted That Met QC Criteria

May 12, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HSR231657

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The data will be stored in Data Archive for the Brain Initiative (DABI) after trial completion. Once submitted to the data repository, we will work with DABI support to ensure that the de-identified KESETT data is available to the public in the DABI search engine where data requests can be submitted.

IPD Sharing Time Frame

The timeline of submission of the public use dataset to the repository will comply with all relevant repository guidelines but in general SIREN will submit data to the repository approximately one year after the primary manuscript of the trial is accepted for publication.

IPD Sharing Access Criteria

Access to the de-identified dataset will be controlled by the data repository. DABI offers two approaches to data access: public or private. The KESETT team plans to make the de-identified data public which means it will be publicly available for downloading to DABI account holders.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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