A Phase 3 interventional study of Levetiracetam (LEV) (60 mg/Kg) + 1 mg/kg Ketamine (KET) and Levetiracetam (LEV) (60 mg/Kg) + 3 mg/kg Ketamine (KET) in Status Epilepticus, sponsored by University of Virginia. Recruiting at 63 sites in United States. Open to participants aged 1 Year and older. Per ClinicalTrials.gov, last updated 2026-09-17.
Sponsored by University of Virginia · Phase 3, Interventional, and Treatment
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.
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.
124 studies on the registry are indexed under Status Epilepticus; 37 are open to participants now.
This study's planned enrollment of 770 is above the median of 80 across 75 interventional studies indexed under Status Epilepticus.
Browse Status Epilepticus studies →University of Virginia is the lead sponsor of 675 studies on the registry; 138 are open to participants now.
Of its 61 completed or terminated interventional studies of FDA-regulated products, 42 (69%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Levetiracetam (LEV) (60 mg/Kg)
Drug: Levetiracetam (LEV) (60 mg/Kg)
LEV 60 mg/mL + 1 mg/mL KET
Drug: Levetiracetam (LEV) (60 mg/Kg) + 1 mg/kg Ketamine (KET)
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.
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 page: Levetiracetam
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.
Termination of SE
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.
Time frame: From 15 minutes after starting the study drug infusion, sustained for 60 minutes without using additional anti-seizure medication.
Desirability of response (DOOR) outcome
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.
Time frame: 60 minutes after starting the study drug infusion
Endotracheal intubation
Endotracheal intubation within 60 minutes of randomization (start of study drug infusion) and duration
Time frame: Within 60 minutes after start of the study drug infusion
ICU duration
ICU duration during the study period for those that are admitted to the ICU as abstracted from the hospital admission record
Time frame: Up to 30 days after enrollment
Hospital length-of-stay (LOS)
Hospital length-of-stay (LOS) from the ED as abstracted from the hospital admission record
Time frame: Up to 30 days after enrollment
Late recurrent seizure
Number of participants with late recurrent seizure between 60 minutes and 4 hours after the start of the study drug infusion
Time frame: Between 60 minutes and 4 hours after the start of the study drug infusion
Time to termination of seizures
The interval from the start of infusion of study drug to the cessation of electrographic seizure in those who meet the primary outcome
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
Late seizures after requiring an anesthetic
Number of participants with late seizures after requiring an anesthetic between 60 minutes and 24 hours after start of study drug infusion
Time frame: Between 60 minutes and 24 hours after start of study drug infusion
All cause mortality
All cause mortality to end of study
Time frame: From the start of study drug infusion to hospital discharge or day 30
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Plan to share: Yes — 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.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
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.
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.
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Studies of the drug tested here: Levetiracetam