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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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 e
• Препарат 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 e
• Препарат 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 e

Первичные конечные точки

• Termination of SE [Срок оценки: From 15 minutes after starting the study drug infusion, sustained for 60 minutes without using additional anti-seizure medication.]

Вторичные конечные точки (8)

• Desirability of response (DOOR) outcome [Срок оценки: 60 minutes after starting the study drug infusion]
• Endotracheal intubation [Срок оценки: Within 60 minutes after start of the study drug infusion]
• ICU duration [Срок оценки: Up to 30 days after enrollment]
• Hospital length-of-stay (LOS) [Срок оценки: Up to 30 days after enrollment]
• Late recurrent seizure [Срок оценки: Between 60 minutes and 4 hours after the start of the study drug infusion]
• Time to termination of seizures [Срок оценки: 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 [Срок оценки: Between 60 minutes and 24 hours after start of study drug infusion]
• All cause mortality [Срок оценки: From the start of study drug infusion to hospital discharge or day 30]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 52 центра

• Banner University Medical Center - Tucson Campus — Tucson
• Ronald Reagan UCLA Medical Center — Los Angeles
• Children's Hospital Los Angeles — Los Angeles
• Stanford University Medical Center — Palo Alto
• UC Davis Medical Center — Sacramento
• San Francisco General Hospital — San Francisco
• UCSF Medical Center — San Francisco
• Yale New Haven Hospital — New Haven
• … и ещё 44 центра

Идентификаторы

NCT: NCT06907173 · HSR231657

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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