Effectiveness of Combined Levetiracetam and Midazolam in Treatment of Generalized Convulsive Status Epilepticus in Children
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Sohag University
- Enrollment
- 144
- Locations
- 1
- Primary Endpoint
- Cessation of seizures
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Each enrolled child will be assigned a unique identification number. Pharmacy will fill the active and placebo preparations in similar containers with sealed code for identification. Participants' families, treating clinicians, and investigators will be unaware of group assignment and drug/placebo therapy.
Eligibility Criteria
- Ages
- 1 Month to 16 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Study group
Children receiving levetiracetam + midazolam
Intervention: Levetiracetam (Drug)
Study group
Children receiving levetiracetam + midazolam
Intervention: Midazolam (Drug)
Control group
Children receiving placebo + midazolam
Intervention: Midazolam (Drug)
Control group
Children receiving placebo + midazolam
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Cessation of seizures
Time Frame: 20 minutes
Cessation of clinical seizures at 20 minutes timepoint (end of first therapy phase)
Secondary Outcomes
- Need for repeating midazolam(20 minutes)
- Cessation of seizures(40 minutes)
- Seizure control(24 hours)
- Need for mechanical ventilation(24 hours)
- Skin rash(24 hours)
- Hypotension(24 hours)
- Agitation/aggression(24 hours)
- Mortality(24 hours)
Investigators
Ahmed Abdelhamid Elshater
Pediatric Resident
Sohag University