Clinical trial NCT06907173: Ketamine add-on Therapy for Established Status Epilepticus Treatment Trial (KESETT)
Official title: Ketamine add-on Therapy for Established Status Epilepticus Treatment Trial (KESETT)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Status Epilepticus
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: University of Michigan
name: Medical University of South Carolina
name: Massachusetts General Hospital
name: Children's National Research Institute
First posted: 2025-04-02
Enrollment: 770
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Termination of SE
timeFrame: From 15 minutes after starting the study drug infusion, sustained for 60 minutes without using additional anti-seizure medication.
Secondary outcomes:
measure: Desirability of response (DOOR) outcome
timeFrame: 60 minutes after starting the study drug infusion
measure: Endotracheal intubation
timeFrame: Within 60 minutes after start of the study drug infusion
measure: ICU duration
timeFrame: Up to 30 days after enrollment
measure: Hospital length-of-stay (LOS)
timeFrame: Up to 30 days after enrollment
measure: Late recurrent seizure
timeFrame: Between 60 minutes and 4 hours after the start of the study drug infusion
measure: Time to termination of seizures
timeFrame: From the start of infusion of study drug to the cessation of electrographic seizure assessed up to 60 minutes from study drug initiation
measure: Late seizures after requiring an anesthetic
timeFrame: Between 60 minutes and 24 hours after start of study drug infusion
measure: All cause mortality
timeFrame: From the start of study drug infusion to hospital discharge or day 30
Other outcomes:
Locations:
Study officials:
affiliation: University of Virginia
name: Jaideep Kapur, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: