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

Sohag University

Status and phase: Completed; Phase 2

Conditions: Status Epilepticus; Status Epilepticus, Generalized Convulsive; Status Epilepticus, Generalized; Generalized Convulsive Status Epilepticus

Treatments: Drug: Placebo; Drug: Levetiracetam; Drug: Midazolam

Study type: Interventional

Funder types: Other

Identifiers

NCT04926844

Soh-Med-21-06-07

Details and patient eligibility

About

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.

Full 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.

Enrollment: 144 patients

Sex: All

Ages: 1 month to 16 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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144 participants in 2 patient groups, including a placebo group

Study group

Experimental group

Description:

Children receiving levetiracetam + midazolam

Treatment:

Drug: Levetiracetam

Drug: Midazolam

Control group

Placebo Comparator group

Description:

Children receiving placebo + midazolam

Treatment:

Drug: Placebo

Drug: Midazolam