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.
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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
124
Intravenous ketamine (5 mg/ml concentration) 2 mg/kg (max 90 mg) over 2 minutes
Intravenous levetiracetam (50 mg/ml concentration) 60 mg/kg (max 4500 mg) over 5 minutes
Intravenous isotonic saline 0.4 mL/kg (maximum 18 mL) over 2 minutes
Department of Pediatrics at Sohag University Hospital
Sohag, Egypt
RECRUITINGNumber of participants with cessation of seizures at 20-minute
Number of participants with cessation of clinically evident seizures at 20-minute after starting study drug administration without endotracheal intubation or need for other antiseizure medications or anticonvulsant sedatives
Time frame: 20 minutes
Number of participants with cessation of seizures at 5-minute
Number of participants with cessation of clinically evident seizures at 5-minute after starting study drug administration
Time frame: 5 minutes
Number of participants with sustained cessation of seizures
Number of participants with sustained cessation of clinically evident seizures from 20-minute to 60-minute after study drug administration with improved responsiveness (verbal communication, obeying commands, or purposeful reaction to painful stimuli) and no endotracheal intubation or use of any additional antiseizure medications or anticonvulsant sedatives.
Time frame: From 20 minutes to 60 minutes
Number of participants with recurrence of seizures
Number of participants with recurrence of clinically evident seizures after initial control
Time frame: From 20 minutes to 4 hours
Number of participants underwent endotracheal intubation
Number of participants underwent endotracheal intubation at 60 minutes after starting study drug administration
Time frame: 60 minutes
Number of participants with severe hypotension
Number of participants with severe hypotension at 60 minutes after starting study drug administration
Time frame: 60 minutes
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Number of participants with severe hypertension
Number of participants with severe hypertension at 60 minutes after starting study drug administration
Time frame: 60 minutes
Number of participants with severe cardiac arrhythmia
Number of participants with severe cardiac arrhythmia at 60 minutes after starting study drug administration
Time frame: 60 minutes
Number of participants with emergence reactions
Emergence reactions (hallucination, delirium, vivid dreams, blurred/double vision, hypersalivation) requiring benzodiazepines or other therapies within 4 hours after starting study drug administration
Time frame: 4 hours
Number of participants admitted to Pediatric Intensive Care Unit
Number of participants with admitted to Pediatric intensive Care Unit at 24 hours after starting study drug administration
Time frame: 24 hours
Mortality
All-cause mortality at 24 hours after starting study drug administration
Time frame: 24 hours