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

NCT ID: NCT07046611

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-02
• Study Completion Date: 2026-07-01

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ketamine + Levetiracetam

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

Intravenous ketamine (5 mg/ml concentration) 2 mg/kg (max 90 mg) over 2 minutes

Levetiracetam

Intervention Type: DRUG

Intravenous levetiracetam (50 mg/ml concentration) 60 mg/kg (max 4500 mg) over 5 minutes

Placebo + Levetiracetam

Group Type: PLACEBO_COMPARATOR

Levetiracetam

Intervention Type: DRUG

Intravenous levetiracetam (50 mg/ml concentration) 60 mg/kg (max 4500 mg) over 5 minutes

Placebo

Intervention Type: DRUG

Intravenous isotonic saline 0.4 mL/kg (maximum 18 mL) over 2 minutes

Interventions

Ketamine

Intravenous ketamine (5 mg/ml concentration) 2 mg/kg (max 90 mg) over 2 minutes

Intervention Type: DRUG

Levetiracetam

Intravenous levetiracetam (50 mg/ml concentration) 60 mg/kg (max 4500 mg) over 5 minutes

Intervention Type: DRUG

Placebo

Intravenous isotonic saline 0.4 mL/kg (maximum 18 mL) over 2 minutes

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age from 1 year to 16 years.
• Generalized convulsive status epilepticus (GCSE), defined as clinically observed generalized tonic-clonic convulsions that continue or recur without complete regaining of consciousness in between for longer than 5 minutes.
• Benzodiazepine-refractory, defined as continuous or recurrent GCSE in the emergency room after receiving an adequate benzodiazepine dose, with the last dose administered within 5 to 30 minutes.

Exclusion Criteria

• Failure to obtain informed consent.
• Prior treatment with antiseizure medication or anticonvulsant sedatives other than benzodiazepines for the presenting GCSE episode.
• Endotracheal intubation before enrollment.
• Acute traumatic brain injury.
• Cardiac arrest/post-anoxic seizures
• Hypoglycemia or hyperglycemia.
• Known allergies or contraindications to ketamine or levetiracetam
• Failure to obtain intravenous access.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sohag University

OTHER

Sponsor Role: lead

Responsible Party

Elsayed Abdelkreem

Assistant Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Pediatrics at Sohag University Hospital

Sohag, , Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

Elsayed Abdelkreem, MD, PhD

Role: CONTACT

d.elsayedmohammed@med.sohag.edu.eg

1114232126 ext. +20

Facility Contacts

Abdelrahim A Sadek, MD, PhD

Role: primary

abdoneurology@yahoo.com

Other Identifiers

Soh-Med-25-6-2PD

Identifier Type: -

Identifier Source: org_study_id