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

NCT ID: NCT06907173

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 770 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2029-12-31

Brief Summary

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.

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.

Conditions

Status Epilepticus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Levetiracetam

Levetiracetam (LEV) (60 mg/Kg)

Group Type: ACTIVE_COMPARATOR

Levetiracetam (LEV) (60 mg/Kg)

Intervention Type: DRUG

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.

Levetiracetam + low dose Ketamine

LEV 60 mg/mL + 1 mg/mL KET

Group Type: EXPERIMENTAL

Levetiracetam (LEV) (60 mg/Kg) + 1 mg/kg Ketamine (KET)

Intervention Type: DRUG

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.

Levetiracetam + high dose Ketamine

LEV 60 mg/mL + 3 mg/mL KET increasing up to a weight of 75 kg

Group Type: EXPERIMENTAL

Levetiracetam (LEV) (60 mg/Kg) + 3 mg/kg Ketamine (KET)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan

OTHER

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Children's National Research Institute

OTHER

Sponsor Role: collaborator

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Jaideep Kapur, MD

Eugene Meyer III Professor of Neuroscience and Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jaideep Kapur, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

Arthur M. Blank Hospital

Georgia, Alabama, United States

Banner University Medical Center - Tucson Campus

Tucson, Arizona, United States

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

UC Davis Medical Center

Sacramento, California, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

Christiana Hospital

Newark, Delaware, United States

Nemours Children's Hospital

Wilmington, Delaware, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Grady Memorial Hospital

Atlanta, Georgia, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

Comer Children's Hospital

Chicago, Illinois, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Michigan University Hospital

Ann Arbor, Michigan, United States

SUNY Upstate Medical University

Syracuse, New York, United States

Duke Regional Hospital

Durham, North Carolina, United States

Duke University Hospital

Durham, North Carolina, United States

Oregon Health & Science University Hospital

Portland, Oregon, United States

Temple University Hospital

Philadelphia, Pennsylvania, United States

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, United States

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Reading Hospital

West Reading, Pennsylvania, United States

Children's Medical Center Dallas

Dallas, Texas, United States

University of Utah Healthcare

Salt Lake City, Utah, United States

University of Virginia Medical Center

Charlottesville, Virginia, United States

Harborview Medical Center

Seattle, Washington, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Central Contacts

Megan Wardius

Role: CONTACT

mew5j@virginia.edu

434-243-6768

Facility Contacts

Claudia Morris, MD

Role: primary

claudia.r.morris@emory.edu

404-785-7070

Aaron Leetch, MD

Role: primary

aleetch@arizona.edu

520-621-8752

Richelle Cooper, MD

Role: primary

rcooper@mednet.ucla.edu

424-440-0486

Ara Festekjian, MD

Role: primary

afestekjian@chla.usc.edu

323-804-8142

Daniel Nishijima, MD

Role: primary

dnishijima@ucdavis.edu

916-734-5010

Charles Wira, MD

Role: primary

charles.wira@yale.edu

203-785-5781

Jason Nomura, MD

Role: primary

jnomura@christianacare.org

302-733-4113

Amy Thompson, MD

Role: primary

amy.thompson@nemours.org

302-490-4146

James Chamberlain, MD

Role: primary

jchamber@childrensnational.org

202-476-8877

Jonathan Ratcliff, MD, MPH

Role: primary

jonathan.ratcliff@emoryhealthcare.org

404-778-1762

Peter Pruitt, MD

Role: primary

peter.pruitt@nm.org

312-694-7000

David Beiser, MD

Role: primary

dbeiser@medicine.bsd.uchicago.edu

773-834-4135

David Beiser, MD

Role: primary

dbeiser@medicine.bsd.uchicago.edu

773-834-4135

Michael Filbin, MD

Role: primary

mfilbin@mgh.harvard.edu

617-724-4758

Mariama Runcie, MD

Role: primary

runciema@med.umich.edu

734-232-2145

Lindsay Nausin, DO

Role: primary

nausinl@upstate.edu

315-464-4363

Alexander Limkakeng, MD

Role: primary

alexander.limkakeng@duke.edu

919-681-0908

Alexander Limkakeng, MD

Role: primary

alexander.limkakeng@duke.edu

919-681-0908

Bory Kea, MD

Role: primary

kea@ohsu.edu

503-494-8083

Derek Isenberg, MD

Role: primary

derek.isenberg@tuhs.temple.edu

215-707-0222

David Barton, MD

Role: primary

bartond2@upmc.edu

412-647-9047

Robert Hickey, MD

Role: primary

robert.hickey@chp.edu

412-692-6567

Adam Sigal, MD

Role: primary

adam.sigal@towerhealth.org

484-628-7016

Pamela Okada, MD

Role: primary

pamela.okada@utsouthwestern.edu

214-456-7000 ext. 67102

Scott Youngquist, MD

Role: primary

scott.youngquist@utah.edu

801-349-0241

Thomas Hartka, MD

Role: primary

trh6u@uvahealth.org

434-924-2897

Vasisht Srinivasan, MD

Role: primary

vasishts@uw.edu

585-730-3843

Keli Coleman, MD

Role: primary

kcoleman@mcw.edu

414-266-2767

Other Identifiers

HSR231657

Identifier Type: -

Identifier Source: org_study_id