Efficacy of Ketamine Infusion Compared With Traditional Anti-epileptic Agents in Refractory Status Epilepticus

Ketamine

Brief Summary

The study will investigate the efficacy of the N-methyl-D-aspartate receptor antagonist ketamine as a first line agent in refractory status epilepticus versus traditional general anesthetic agents used for burst suppression that target the gamma-aminobutyric acid adrenergic receptors.

Intervention / Treatment

  • Traditional Treatment (Group T) (DRUG)
    Patients will receive traditional drug infusions
  • Ketamine Infusion (Group K) (DRUG)
    Patients will receive loading dose of 2.5 mg/kg of ketamine followed by a continuous infusion with a starting dose of 3mg/kg/hr with titration in 1mg/kg/hr increments until burst suppression is achieved or a maximum dose of 10mg/kg/hr is reached

Condition or Disease

  • Refractory Epilepsy

Phase

  • Phase 2
  • Phase 3

    • Study Design

    Study type: INTERVENTIONAL
    Status: Withdrawn
    Study results: No Results Available
    Age: 18 Years to 100 Years
    Enrollment: 0 (ACTUAL)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Prevention

    Masking

    SINGLE:
    • Participant

    Clinical Trial Dates

    Start date: May 04, 2017 ACTUAL
    Primary Completion: Dec 31, 2019 ACTUAL
    Completion Date: May 18, 2021 ACTUAL
    Study First Posted: Apr 14, 2017 ACTUAL
    Results First Posted: Aug 31, 2020
    Last Updated: May 18, 2021

    Sponsors / Collaborators

    Lead Sponsor: University of Alabama at Birmingham
    Responsible Party: N/A

    Location

    Birmingham, Alabama, USA

    The traditional treatment for refractory status epilepticus includes diazepam, midazolam, valproic acid, thiopental and propofol. These medications fail to control seizure activity in 20-40% of patients. This is attributed to decrease in activity of gamma-aminobutyric acid receptors along with reciprocal up regulation of N-Methyl-D-aspartate receptors. Glutamate activation of N-methyl-D-aspartate receptors promotes calcium influx and excitotoxicity. Ketamine, an intravenous anesthetic agent which is a non-competitive antagonist of N-methyl-D-aspartate receptors can block the flow of Ca and Na and by combining with phencyclidine binding sites inside the ion channel of N-methyl-D-aspartate receptors, reduce the epileptiform burst discharges and after potential. Therefore, targeting the N-methyl-D-aspartate receptors with ketamine may provide a novel approach to control refractory seizures. Moreover, by blocking glutamate mediated N-methyl-D-aspartate receptor induced neurotoxicity, ketamine may render neuroprotection. Ketamine also provides additional advantage of hemodynamic stability. Currently, ketamine is used as a last resort drug in the treatment of refractory status epilepticus.

    The specific aim is to determine whether continuous infusion of ketamine as a first line agent for refractory status epilepticus is effective in controlling seizures.

    The central hypothesis of our proposal is that early treatment with ketamine will be much more efficacious in controlling refractory status compared to the traditional treatment.

    Participant Groups

    • Group T patients will be placed into burst suppression with the traditional drug infusions which include any single or combination of drugs; usually benzodiazepines, barbiturates and or propofol.

    • Patients in the group K arm will receive a loading dose of 2.5 mg/kg of ketamine followed by a continuous infusion with a starting dose of 3mg/kg/hr with titration in 1mg/kg/hr increments until burst suppression is achieved or a maximum dose of 10mg/kg/hr is reached. After 48 hours of burst suppression the ketamine dosage will be reduced by 2mg/kg/hr in a stepwise fashion to evaluated for EEG or clinical evidence of seizure recurrence.

    Eligibility Criteria

    Sex: All
    Minimum Age: 18
    Maximum Age: 100
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    Inclusion Criteria:

    * Patients more than 18 years of age with a diagnosis of status epilepticus
    * Considered for burst suppression therapy after failing 2 or 3 anti-epileptic medications

    Exclusion Criteria:

    * Post anoxic status epilepticus
    * Pregnant women, as confirmed by urine, or blood human chorionic gonadotropin, ultrasound or physical exam
    * Prisoners
    * Age less than 18 years
    * Allergy or sensitivity to the drug in question

    Primary Outcomes

    • Average time for burst suppression

    • Average time for seizures to terminate

    Secondary Outcomes

    • The need of vasopressors

    • Total number of days patient is on the ventilator

    • Total number of days in the ICU

    • Nutrition provided through a feeding tube or catheter

    • MRI scans 7 to 10 days after burst suppression

    • death

    More Details

    NCT Number: NCT03115489
    Other IDs: F151214004
    Study URL: https://clinicaltrials.gov/study/NCT03115489
    Last updated: Sep 29, 2023