Children's National

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

Purpose

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.

Condition

Status Epilepticus

Eligibility

Eligible Ages: Over 1 Year
Eligible Sex: All
Accepts Healthy Volunteers: No

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 Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

Arm	Description	Assigned Intervention
Active Comparator Levetiracetam	Levetiracetam (LEV) (60 mg/Kg)	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. 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. 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.

Recruiting Locations

Children's National and nearby locations

Children's National Medical Center
Washington D.C., District of Columbia 20010

Contact:
James Chamberlain, MD
202-476-8877
jchamber@childrensnational.org

More Details

NCT ID: NCT06907173
Status: Recruiting
Sponsor: University of Virginia

Study Contact

Megan Wardius
434-243-6768
mew5j@virginia.edu

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.