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

• ClinicalTrials.gov Identifier: NCT03115489
• Recruitment Status: Withdrawn
• First Posted: April 14, 2017
• Last Update Posted: May 21, 2021
• Sponsor: University of Alabama at Birmingham
• Information provided by (Responsible Party): Vinodkumar Singh, University of Alabama at Birmingham

Tracking Information

• First Submitted Date: April 10, 2017
• First Posted Date: April 14, 2017
• Last Update Posted Date: May 21, 2021
• Actual Study Start Date: May 4, 2017
• Actual Primary Completion Date: December 31, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy of Ketamine Infusion Compared With Traditional Anti-epileptic Agents in Refractory Status Epilepticus
• Official Title: 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: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Prevention
• Condition: Refractory Epilepsy

Intervention

• 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

• 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.

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: May 18, 2021): 0
• Original Estimated Enrollment (submitted: April 10, 2017): 32
• Actual Study Completion Date: May 18, 2021
• Actual Primary Completion Date: December 31, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03115489
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Responsible Party: Vinodkumar Singh, University of Alabama at Birmingham
• Study Sponsor: University of Alabama at Birmingham
• Collaborators: Not Provided

Investigators

• Principal Investigator: Vinodkumar Singh, MD; University of Alabama at Birmingham

• PRS Account: University of Alabama at Birmingham
• Verification Date: May 2021