Effectiveness of Combined Levetiracetam and Midazolam in Generalized Convulsive Status Epilepticus in Children

Phase 2

Completed

• Conditions: Generalized Convulsive Status Epilepticus; Status Epilepticus, Generalized; Status Epilepticus, Generalized Convulsive; Status Epilepticus
• Interventions: Drug: Levetiracetam; Drug: Midazolam; Drug: Placebo

• Registration Number: NCT04926844
• Lead Sponsor: Sohag University

Brief Summary

Generalized status epilepticus is a common pediatric neurological emergency with significant mortality and morbidity. Benzodiazepines remain the first anticonvulsive line but benzo-diazepines don't control seizures in about 30% of cases. GCSE may be more rapidly stopped and controlled through combining another drug with benzodiazepines such as Levetiracetam, acting by different pathways. This study aims to evaluate the effectiveness of combined levetiracetam and midazolam in treatment of generalized convulsive status epilepticus in children.

Detailed Description

Generalized convulsive status epilepticus (GCSE) is a common pediatric neurological emergency with an annual incidence of up to 73 episodes per 100,000 children and is associated with mortality in 2.7% of cases and overall morbidity in 10% - 20% of cases, including hemodynamic instability and long-term neurological impairments.

The management of GCSE in children starts with emergency measures (stabilization phase) with monitoring and laboratory testing in the first 5 minutes. Benzodiazepines are used as first-line anticonvulsants for GCSE that persists for more than 5 minutes. However, studies have shown that benzo-diazepines don't control GCSE in about 30% of patients. GCSE may be more rapidly stopped and controlled through combining another drug with benzodiazepines, acting by different pathways.

Levetiracetam is a recent broad-spectrum antiepileptic drug with a relatively high safety profile. The effectiveness of intravenous levetiracetam has been demonstrated as a second-line anticonvulsant in GCSE. In this study, we aim to evaluate the effectiveness and safety of levetiracetam plus midazolam versus midazolam alone as first-line therapy of GCSE in children.

Study Timeline

• Study First Submitted: 2021-06-14
• Study First Submitted QC: 2021-06-14
• Study First Posted: 2021-06-15
• Study Start: 2021-06-20
• Primary Completion: 2022-08-30
• Status Verified: 2022-09
• Study Completion: 2022-09-01
• Last Update Submitted: 2022-09-17
• Last Update Posted: 2022-09-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 144

Inclusion Criteria

• Generalized convulsive status epilepticus, which is clinically defined at the time of presentation as continuous, generalized, tonic-clonic seizure activity or ≥ 2 generalized tonic-clonic seizures without recovery of consciousness for more than 5 minutes.

Exclusion Criteria

• Failure to obtain informed consent.
• Prior therapy with any anticonvulsant for the presenting episode of generalized convulsive status epilepticus.
• Epileptic patients on levetiracetam therapy.
• Known allergy or contraindications to any of the study drugs.
• End-stage kidney disease.
• Severe liver disease.
• Cardiac diseases.
• Hypoglycemia or hyperglycemia.
• Inborn errors of metabolism.
• Known mood/behavioral disorder.
• Failure to obtain intravenous access in the first 5 minutes.
• Cessation of seizures during the stabilization phase (0 - 5 minutes).
• Traumatic brain injury

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study group	Levetiracetam	Children receiving levetiracetam + midazolam
Control group	Midazolam	Children receiving placebo + midazolam
Control group	Placebo	Children receiving placebo + midazolam
Study group	Midazolam	Children receiving levetiracetam + midazolam

Primary Outcome Measures

Name	Time	Method
Cessation of seizures	20 minutes	Cessation of clinical seizures at 20 minutes timepoint (end of first therapy phase)

Secondary Outcome Measures

Name	Time	Method
Cessation of seizures	40 minutes	Cessation of clinical seizures at 40 minutes timepoint (end of second therapy phase).
Need for repeating midazolam	20 minutes	Need for repeating midazolam during the first therapy phase (5 - 20 min)
Seizure control	24 hours	24-hours seizure control (no visually observed recurrence of seizures after the end of second phase therapy with improved sensorium)
Need for mechanical ventilation	24 hours	Need for mechanical ventilation
Skin rash	24 hours	Occurrence of skin rash
Hypotension	24 hours	Occurrence of hypotension
Agitation/aggression	24 hours	Occurrence of agitation/aggression
Mortality	24 hours	Occurrence of death

Trial Locations

Locations (1)

Department of Pediatrics - Sohag University Hospital; 🇪🇬 Sohag, Egypt