NCT07046611

Ketamine and Levetiracetam as Second-line Antiseizure Medication for Status Epilepticus in Children

Efficacy of Combined Ketamine and Levetiracetam as a Second-line Anti-seizure Medication for Generalized Convulsive Status Epilepticus in Children

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 124 (estimated)
• Sponsor: Sohag University · Academic / Other
• Sex: All
• Age: 1 Year – 16 Years
• Healthy volunteers: Not accepted

Summary

About 40% of children with generalized convulsive status epilepticus (GCSE) are not terminated by first-line benzodiazepines (BDZs), and approximately 50% of BDZ-refractory GCSE are not controlled by second-line antiseizure medications. This study investigates the efficacy of ketamine-levetiracetam combination vs. levetiracetam alone for treating children with BDZ-refractory GCSE.

Detailed description

Generalized convulsive status epilepticus (GCSE) is the most common pediatric neurological emergency. Benzodiazepines (BDZs) are the recommended first-line anti-seizure medication (ASM) for GCSE, but they fail to halt seizures in about 40% of cases. Moreover, approximately 50% of BDZ-refractory GCSE are not terminated by second-line ASMs, including levetiracetam, valproate, and phenytoin. Continuous GCSE for a longer duration is associated with progressive brain injury and a higher risk of mortality, epilepsy, and permanent neurodevelopmental impairment. Therefore, early control of GCSE is pivotal for improving patients' outcomes. A potential approach for early control of GCSE is the use of early ASM polytherapy. Ketamine is a promising option to be combined with standard ASMs for more rapid control of seizures. Ketamine has been used for decades for pediatric procedural analgosedation due to its excellent safety profile and wide therapeutic index. Ketamine works as a noncompetitive antagonist for N-methyl-D-aspartate (NMDA) receptors, which are progressively upregulated by way of receptor trafficking during ongoing seizure activity. Ketamine administration is associated with termination or attenuation of refractory SE (RSE) and super-refractory SE (SRSE). Multiple observational studies have reported the efficacy of ketamine in the pre-hospital emergency treatment of BZD-refractory status epilepticus. Furthermore, the recently published Ket-Mid study demonstrated that the ketamine-midazolam combination was more effective than midazolam alone in the initial treatment of pediatric GCSE. However, the value of combining ketamine with levetiracetam for the treatment of BZD-refractory status epilepticus has not been well investigated. The present study (Ketamine and Levetiracetam as Second-line antiseizure medication for Status Epilepticus in Children, KLaSSEC) aims to investigate the efficacy of ketamine-levetiracetam combination vs. levetiracetam alone for treating children with BDZ-refractory GCSE. The findings could help earlier control of seizures and better clinical outcomes for children with status epilepticus

Conditions

• Generalized Convulsive Status Epilepticus

Interventions

Type	Name	Description
DRUG	Ketamine	Intravenous ketamine (5 mg/ml concentration) 2 mg/kg (max 90 mg) over 2 minutes
DRUG	Levetiracetam	Intravenous levetiracetam (50 mg/ml concentration) 60 mg/kg (max 4500 mg) over 5 minutes
DRUG	Placebo	Intravenous isotonic saline 0.4 mL/kg (maximum 18 mL) over 2 minutes

Timeline

• Start date: 2025-07-02
• Primary completion: 2026-06-30
• Completion: 2026-07-01
• First posted: 2025-07-01
• Last updated: 2025-07-03

Locations

1 site across 1 country: Egypt