Phenobarbital Versus Valproate for Generalized Convulsive Status Epilepticus

Study Overview
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Brief Summary
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Although generalized convulsive status epilepticus (GCSE) is a life-threatening emergency, evidence-based data to guide initial drug treatment choices are lacking in the Chinese population. The investigators conduct this prospective randomized controlled trial to evaluate the relative efficacy and safety of intravenous (IV) phenobarbital (PB) and valproate (VPA) in patients with GCSE.

Detailed Description
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After the failure of first-line diazepam treatment, patients with GCSE are randomized to receive either IV PB (standard doses, low rate) or VPA (standard). Successful treatment is considered when clinical and electroencephalographic seizure activity ceases. Adverse events following treatment and the neurological outcomes at discharge and 3 months later are also evaluated.

Official Title
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Phenobarbital Versus Valproate for Generalized Convulsive Status Epilepticus in Adults: A Prospective Randomized Controlled Trial in China

Conditions
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Generalized Convulsive Status Epilepticus

Intervention / Treatment
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* Drug: Phenobarbital
* Drug: Valproate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All consecutive GCSE patients (after the failure of first-line diazepam treatment) who were admitted in the emergency room or neurocritical care unit in Xuanwu Hospital of Capital Medical University. Exclusion Criteria: Unstable vital signs, such as a systolic blood pressure of <90 mm Hg, a pulse of <60 beats per min, or an arterial blood oxygen saturation of <90%, Liver dysfunction (alanine transaminase or total bilirubin of more than twice the normal upper limit), Neurologic emergency requiring immediate surgical intervention, Pregnancy or breast feeding, Hypersensitivity to study drugs.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phenobarbital<br>In the PB group, a loading dose of 20 mg/kg (may give an additional 10 mg/kg) begins at a rate of 50 mg/min followed by IV 100 mg q6 h. | Drug: Phenobarbital<br>* In the PB group, a loading dose of 20 mg/kg (may give an additional 10 mg/kg) begins at a rate of 50 mg/min followed by IV 100 mg q6 h.<br>* Other names: Luminal;|
| Experimental: Valproate<br>In the VPA group, a loading dose of 30 mg/kg (may give an additional 15 mg/kg) begins at a rate of 3 mg/kg per min followed by a continuous infusion at a rate of 1-2 mg/kg per hour. | Drug: Valproate<br>* In the VPA group, a loading dose of 30 mg/kg (may give an additional 15 mg/kg) begins at a rate of 3 mg/kg per min followed by a continuous infusion at a rate of 1-2 mg/kg per hour.<br>* Other names: Depakine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with effective seizure control | The primary study endpoint is the number of patients with effective seizure control, defined as a cessation of clinical and electroencephalographic seizure activity within 1 h after administration of the phenobarbital or valproate loading dose. Effective control of GCSE is assessed clinically by one certified neurologist and also confirmed with EEG by one certified electroencephalographer. | One hour after the end of the PB or VPA loading dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality of patients | Neurologic outcome is assessed both at 30 days and at 3 months by one physician unaware of the therapeutic assignment through a phone interview or scheduled follow-up clinic visit. Mortality of each group is recorded at 30 days and at 3 months, respectively. | at 30 days and at 3 months | 
| Number of patients with post-SE symptomatic epilepsy | Post-SE symptomatic epilepsy at 3 months is analyzed. It is defined as the occurrence of at least 2 unprovoked epileptic seizure occurring not earlier than 4 weeks after termination of SE in those without pre-existing epilepsy. | 3 months | 
| The relapse rates of SE and nonconvulsive status epilepticus (NCSE) / nonconvulsive seizures (NCS) | The investigators also record the relapse rates of SE and nonconvulsive status epilepticus (NCSE) / nonconvulsive seizures (NCS) in each group in the first 24 h. | in the first 24 h |