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

NCT ID: NCT03115489

Last Updated: 2021-05-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2/PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-04
• Study Completion Date: 2021-05-18

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.

Conditions

Refractory Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Traditional Treatment (Group T)

Intervention Type: DRUG

Patients will receive traditional drug infusions

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.

Group Type: ACTIVE_COMPARATOR

Ketamine Infusion (Group K)

Intervention Type: 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

Interventions

Traditional Treatment (Group T)

Patients will receive traditional drug infusions

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

benzodiazepines, barbiturates, propofol; Ketalar

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Vinodkumar Singh

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Vinodkumar Singh, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

UAB Department of Anesthesiology and Perioperative Medicine

Birmingham, Alabama, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 30232735 (View on PubMed)

Other Identifiers

F151214004

Identifier Type: -

Identifier Source: org_study_id