Clinical trial NCT03115489: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: Refractory Epilepsy
Keywords: seizure
glutamate activation
N-Methyl D-Aspartate
gamma-aminobutyric acid receptor
Ketamine
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2017-04-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Time taken for burst suppression
timeFrame: Baseline to 1 hr
measure: Time taken for termination of seizures
timeFrame: Baseline to 24 hrs
Secondary outcomes:
measure: Use of vasopressors
timeFrame: baseline to 72 hrs
measure: Number of days on ventilator
timeFrame: Baseline to 72 hrs
measure: Length of stay in ICU
timeFrame: Baseline to 72 hrs postoperatively
measure: Use of parenteral or enteral nutrition
timeFrame: Baseline to 72 hrs postoperatively
measure: Medical imaging results
timeFrame: Post-op Day 2 to Post-op day 10
measure: Mortality
timeFrame: baseline to post-op day 10
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Department of Anesthesiology and Perioperative Medicine
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Vinodkumar Singh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.