Phenobarbital Versus Valproate for Generalized Convulsive Status Epilepticus

July 8, 2019 updated by: Yingying Su, Xuanwu Hospital, Beijing

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100053
    • Fujian
      • Xiamen, Fujian, China
        • Recruiting
        • Zhongshan Hospital, Xiamen University
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China
        • Recruiting
        • Nanfang Hospital, Southern Medical University
        • Contact:
    • Hunan
      • Changsha, Hunan, China
        • Recruiting
        • Xiangya Hospital, Central South University
        • Contact:
    • Xi'an
    • Yunnan
      • Kunming, Yunnan, China
        • Recruiting
        • The First People's Hospital of Yunnan Province
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.
Other Names:
  • Luminal
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.
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.
Other Names:
  • Depakine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
One hour after the end of the PB or VPA loading dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
at 30 days and at 3 months
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.
3 months
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.
in the first 24 h

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events
Time Frame: From the administration of PB or VPA to 1 week
Adverse events are recorded as follows: systolic blood pressure lower than 90 mmHg, pulse lower than 50 beats/ min, arrhythmia (except supraventricular tachycardia), respiratory depression (arterial oxygen saturation below 90%, partial pressure of oxygen below 60 mmHg, or partial pressure of carbon dioxide above 60 mmHg), drug-induced liver disease (alanine aminotransferase or total bilirubin increase of more than twice the upper limit of the normal range), elevation of blood ammonia (more than twice the upper limit of the normal range), gastric motility insufficiency, bone marrow suppression (leukocytopenia, neutrocytopenia, thrombocytopenia or anemia), coagulation disorders, or drug-related sedation. The time to record adverse events is from the administration of PB or VPA to 1 week.
From the administration of PB or VPA to 1 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xuanwu Hospital, Beijing

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 16, 2017

Primary Completion (Anticipated)

October 1, 2019

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

November 15, 2016

First Submitted That Met QC Criteria

January 16, 2017

First Posted (Estimate)

January 20, 2017

Study Record Updates

Last Update Posted (Actual)

July 9, 2019

Last Update Submitted That Met QC Criteria

July 8, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WEIBANYIZHENGHAN[2012]649

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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