Phenobarbital Versus Valproate for Generalized Convulsive Status Epilepticus

Generalized Convulsive Status Epilepticus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03025906
• Other study ID #: WEIBANYIZHENGHAN[2012]649
• Status: Recruiting
• Phase: Phase 2
• Start date: February 16, 2017
• Est. completion date: December 2019

Study information

• Verified date: July 2019
• Source: Xuanwu Hospital, Beijing
• Contact: Su Yingying
• Phone: 15901361953
• Email: tangsuyingying[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 2019
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Generalized Convulsive Status Epilepticus
• Status Epilepticus

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Xuanwu Hospital	Beijing	Beijing
China	Xiangya Hospital, Central South University	Changsha	Hunan
China	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	The First People's Hospital of Yunnan Province	Kunming	Yunnan
China	Xijing Hospital	Shanxi	Xi'an
China	Zhongshan Hospital, Xiamen University	Xiamen	Fujian

Sponsors (1)

Lead Sponsor	Collaborator
Xuanwu Hospital, Beijing

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Adverse Events	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
Primary	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	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
Secondary	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
Secondary	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