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

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ClinicalTrials.gov Identifier: NCT03115489
Recruitment Status : Recruiting
First Posted : April 14, 2017
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Vinodkumar Singh, University of Alabama at Birmingham

Tracking Information
First Submitted Date  ICMJE April 10, 2017
First Posted Date  ICMJE April 14, 2017
Last Update Posted Date August 14, 2019
Actual Study Start Date  ICMJE May 4, 2017
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 10, 2017)
  • Time taken for burst suppression [ Time Frame: Baseline to 1 hr ]
    Average time for burst suppression
  • Time taken for termination of seizures [ Time Frame: Baseline to 24 hrs ]
    Average time for seizures to terminate
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2017)
  • Use of vasopressors [ Time Frame: baseline to 72 hrs ]
    The need of vasopressors
  • Number of days on ventilator [ Time Frame: Baseline to 72 hrs ]
    Total number of days patient is on the ventilator
  • Length of stay in ICU [ Time Frame: Baseline to 72 hrs postoperatively ]
    Total number of days in the ICU
  • Use of parenteral or enteral nutrition [ Time Frame: Baseline to 72 hrs postoperatively ]
    Nutrition provided through a feeding tube or catheter
  • Medical imaging results [ Time Frame: Post-op Day 2 to Post-op day 10 ]
    MRI scans 7 to 10 days after burst suppression
  • Mortality [ Time Frame: baseline to post-op day 10 ]
    death
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Ketamine Infusion Compared With Traditional Anti-epileptic Agents in Refractory Status Epilepticus
Official Title  ICMJE Efficacy of Ketamine Infusion Compared With Traditional Anti-epileptic Agents in Refractory Status Epilepticus- a Pilot Study
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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Condition  ICMJE Refractory Epilepsy
Intervention  ICMJE
  • Drug: Traditional Treatment (Group T)
    Patients will receive traditional drug infusions
    Other Name: benzodiazepines, barbiturates, propofol
  • Drug: Ketamine Infusion (Group K)
    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
    Other Name: Ketalar
Study Arms  ICMJE
  • Placebo Comparator: Traditional Treatment (Group T)
    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.
    Intervention: Drug: Traditional Treatment (Group T)
  • Active Comparator: Ketamine Infusion (Group K)
    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.
    Intervention: Drug: Ketamine Infusion (Group K)
Publications * Rosati A, De Masi S, Guerrini R. Ketamine for Refractory Status Epilepticus: A Systematic Review. CNS Drugs. 2018 Nov;32(11):997-1009. doi: 10.1007/s40263-018-0569-6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 10, 2017)
32
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Adam Sturdivant, MPH 205-934-4042 Adamsturdivant@uabmc.edu
Contact: Ayesha Bryant, MD 205-996-7383 asbryant@uabmc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03115489
Other Study ID Numbers  ICMJE F151214004
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Vinodkumar Singh, University of Alabama at Birmingham
Study Sponsor  ICMJE University of Alabama at Birmingham
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Vinodkumar Singh, MD University of Alabama at Birmingham
PRS Account University of Alabama at Birmingham
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP