<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03025906</url>
  </required_header>
  <id_info>
    <org_study_id>WEIBANYIZHENGHAN[2012]649</org_study_id>
    <nct_id>NCT03025906</nct_id>
  </id_info>
  <brief_title>Phenobarbital Versus Valproate for Generalized Convulsive Status Epilepticus</brief_title>
  <official_title>Phenobarbital Versus Valproate for Generalized Convulsive Status Epilepticus in Adults: A Prospective Randomized Controlled Trial in China</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xuanwu Hospital, Beijing</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Xuanwu Hospital, Beijing</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Although generalized convulsive status epilepticus (GCSE) is a life-threatening emergency,&#xD;
      evidence-based data to guide initial drug treatment choices are lacking in the Chinese&#xD;
      population. The investigators conduct this prospective randomized controlled trial to&#xD;
      evaluate the relative efficacy and safety of intravenous (IV) phenobarbital (PB) and&#xD;
      valproate (VPA) in patients with GCSE.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After the failure of first-line diazepam treatment, patients with GCSE are randomized to&#xD;
      receive either IV PB (standard doses, low rate) or VPA (standard). Successful treatment is&#xD;
      considered when clinical and electroencephalographic seizure activity ceases. Adverse events&#xD;
      following treatment and the neurological outcomes at discharge and 3 months later are also&#xD;
      evaluated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 16, 2017</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">October 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with effective seizure control</measure>
    <time_frame>One hour after the end of the PB or VPA loading dose</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mortality of patients</measure>
    <time_frame>at 30 days and at 3 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with post-SE symptomatic epilepsy</measure>
    <time_frame>3 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The relapse rates of SE and nonconvulsive status epilepticus (NCSE) / nonconvulsive seizures (NCS)</measure>
    <time_frame>in the first 24 h</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>From the administration of PB or VPA to 1 week</time_frame>
    <description>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.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Generalized Convulsive Status Epilepticus</condition>
  <arm_group>
    <arm_group_label>Phenobarbital</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Valproate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Phenobarbital</intervention_name>
    <description>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.</description>
    <arm_group_label>Phenobarbital</arm_group_label>
    <other_name>Luminal</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Valproate</intervention_name>
    <description>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.</description>
    <arm_group_label>Valproate</arm_group_label>
    <other_name>Depakine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All consecutive GCSE patients (after the failure of first-line diazepam treatment) who&#xD;
             were admitted in the emergency room or neurocritical care unit in Xuanwu Hospital of&#xD;
             Capital Medical University.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unstable vital signs, such as a systolic blood pressure of &lt;90 mm Hg, a pulse of &lt;60&#xD;
             beats per min, or an arterial blood oxygen saturation of &lt;90%,&#xD;
&#xD;
          -  Liver dysfunction (alanine transaminase or total bilirubin of more than twice the&#xD;
             normal upper limit),&#xD;
&#xD;
          -  Neurologic emergency requiring immediate surgical intervention,&#xD;
&#xD;
          -  Pregnancy or breast feeding,&#xD;
&#xD;
          -  Hypersensitivity to study drugs.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Su Yingying</last_name>
    <phone>15901361953</phone>
    <email>tangsuyingying@sina.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Xuanwu Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100053</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Su Yingying</last_name>
      <phone>15901361953</phone>
      <email>tangsuyingying@sina.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Zhongshan Hospital, Xiamen University</name>
      <address>
        <city>Xiamen</city>
        <state>Fujian</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhuang Xiaorong</last_name>
      <email>zxr63@126.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Nanfang Hospital, Southern Medical University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pan Suyue</last_name>
      <email>pansuyue82@qq.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Xiangya Hospital, Central South University</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhang Le</last_name>
      <email>zlzdzlzd@163.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Xijing Hospital</name>
      <address>
        <city>Shanxi</city>
        <state>Xi'an</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jiang Wen</last_name>
      <email>drjiangwen@hotmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The First People's Hospital of Yunnan Province</name>
      <address>
        <city>Kunming</city>
        <state>Yunnan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ding Li</last_name>
      <email>dingli701@sina.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>November 15, 2016</study_first_submitted>
  <study_first_submitted_qc>January 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 20, 2017</study_first_posted>
  <last_update_submitted>July 8, 2019</last_update_submitted>
  <last_update_submitted_qc>July 8, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Xuanwu Hospital, Beijing</investigator_affiliation>
    <investigator_full_name>Yingying Su</investigator_full_name>
    <investigator_title>neurology department</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Status Epilepticus</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Valproic Acid</mesh_term>
    <mesh_term>Phenobarbital</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03025906
org study id: WEIBANYIZHENGHAN[2012]649
nct id: NCT03025906
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Number of patients with effective seizure control
time frame: One hour after the end of the PB or VPA loading dose
description: 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.
measure: Mortality of patients
time frame: at 30 days and at 3 months
description: 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.
measure: Number of patients with post-SE symptomatic epilepsy
time frame: 3 months
description: 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.
measure: The relapse rates of SE and nonconvulsive status epilepticus (NCSE) / nonconvulsive seizures (NCS)
time frame: in the first 24 h
description: 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.
measure: Number of Participants With Adverse Events
time frame: From the administration of PB or VPA to 1 week
description: 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.
arm group label: Phenobarbital
arm group type: Experimental
description: 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.
arm group label: Valproate
arm group type: Experimental
description: 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.
intervention type: Drug
intervention name: Phenobarbital
description: 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.
arm group label: Phenobarbital
other name: Luminal
intervention type: Drug
intervention name: Valproate
description: 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.
arm group label: Valproate
other name: Depakine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Su Yingying
phone: 15901361953
email: tangsuyingying@sina.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Xuanwu Hospital, Beijing
investigator full name: Yingying Su
investigator title: neurology department
mesh term: Status Epilepticus
mesh term: Valproic Acid
mesh term: Phenobarbital
sharing ipd: Undecided