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

Refractory Epilepsy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03115489
• Other study ID #: F151214004
• Status: Withdrawn
• Phase: Phase 2/Phase 3
• Start date: May 4, 2017
• Est. completion date: May 18, 2021

Study information

• Verified date: May 2021
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 18, 2021
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Drug Resistant Epilepsy
• Refractory Epilepsy
• Status Epilepticus

Intervention

Drug:
• Traditional Treatment (Group T)
Patients will receive traditional drug infusions
• 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

Locations

Country	Name	City	State
United States	UAB Department of Anesthesiology and Perioperative Medicine	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time taken for burst suppression	Average time for burst suppression	Baseline to 1 hr
Primary	Time taken for termination of seizures	Average time for seizures to terminate	Baseline to 24 hrs
Secondary	Use of vasopressors	The need of vasopressors	baseline to 72 hrs
Secondary	Number of days on ventilator	Total number of days patient is on the ventilator	Baseline to 72 hrs
Secondary	Length of stay in ICU	Total number of days in the ICU	Baseline to 72 hrs postoperatively
Secondary	Use of parenteral or enteral nutrition	Nutrition provided through a feeding tube or catheter	Baseline to 72 hrs postoperatively
Secondary	Medical imaging results	MRI scans 7 to 10 days after burst suppression	Post-op Day 2 to Post-op day 10
Secondary	Mortality	death	baseline to post-op day 10