Effectiveness of Combined Levetiracetam and Midazolam in Generalized Convulsive Status Epilepticus in Children
Condition: Status Epilepticus; Generalized Convulsive Status Epilepticus; Status Epilepticus, Generalized; Status Epilepticus, Generalized Convulsive
MeSH terms: Status Epilepticus
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Levetiracetam; Midazolam; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Intravenous levetiracetam 60 mg/kg (max 4500 mg) over 5 minutes (diluted with isotonic saline to a concentration of 50 mg/ml).; Intravenous midazolam 0.2 mg/kg (maximum 10 mg) over 2 minutes; Intravenous isotonic saline (1.2 ml/kg) over 5 minutes
Other intervention name(s): Keppra; Tiratam
Intervention MeSH terms: Midazolam; Levetiracetam
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Two groups of children with continuing seizures after stabilization phase (5 minutes):
Study group; will receive intravenous levetiracetam 60 mg/kg (max 4500 mg) over 5 minutes (diluted with isotonic saline to a concentration of 50 mg/ml).
Control group will receive intravenous isotonic saline (as a placebo) in the same way. At the same time, both groups will receive intravenous midazolam 0.2 mg/kg (maximum 10 mg) over 2 minutes.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Status epilepticus; Convulsions; Children; Seizures; Benzodiazepines; Midazolam; Levetiracetam