Phenobarbital Versus Valproate for Generalized Convulsive Status Epilepticus

Overview

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.

Full Title of Study: “Phenobarbital Versus Valproate for Generalized Convulsive Status Epilepticus in Adults: A Prospective Randomized Controlled Trial in China”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Single (Participant)
  • Study Primary Completion Date: October 2019

Detailed Description

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.

Interventions

  • Drug: Phenobarbital
    • 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: Valproate
    • 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.

Arms, Groups and Cohorts

  • Experimental: Phenobarbital
    • 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.
  • Experimental: Valproate
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Number of patients with effective seizure control
    • Time Frame: One hour after the end of the PB or VPA loading dose
    • 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.

Secondary Measures

  • Mortality of patients
    • Time Frame: at 30 days and at 3 months
    • 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.
  • Number of patients with post-SE symptomatic epilepsy
    • Time Frame: 3 months
    • 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.
  • The relapse rates of SE and nonconvulsive status epilepticus (NCSE) / nonconvulsive seizures (NCS)
    • Time Frame: in the first 24 h
    • 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.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Xuanwu Hospital, Beijing
  • Provider of Information About this Clinical Study
    • Principal Investigator: Yingying Su, neurology department – Xuanwu Hospital, Beijing
  • Overall Contact(s)
    • Su Yingying, 15901361953, tangsuyingying@sina.com

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