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

University of Virginia

Status and phase: Begins enrollment in 2 months; Phase 3

Conditions: Status Epilepticus

Treatments: Drug: Levetiracetam (LEV) (60 mg/Kg) + 3 mg/kg Ketamine (KET); Drug: Levetiracetam (LEV) (60 mg/Kg) + 1 mg/kg Ketamine (KET); Drug: Levetiracetam (LEV) (60 mg/Kg)

Study type: Interventional

Funder types: Other

Identifiers

NCT06907173

HSR231657

Details and patient eligibility

About

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.

Full 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.

Enrollment: 770 estimated patients

Sex: All

Ages: 1+ year old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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770 participants in 3 patient groups

Levetiracetam

Active Comparator group

Description:

Levetiracetam (LEV) (60 mg/Kg)

Treatment:

Drug: Levetiracetam (LEV) (60 mg/Kg)

Levetiracetam + low dose Ketamine

Experimental group

Description:

LEV 60 mg/mL + 1 mg/mL KET

Treatment:

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

Levetiracetam + high dose Ketamine

Experimental group

Description:

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

Treatment:

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