<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/NCT02241616</url>
  </required_header>
  <id_info>
    <org_study_id>SGHLC20140818002</org_study_id>
    <nct_id>NCT02241616</nct_id>
  </id_info>
  <brief_title>Traditional Chinese Medicine Combined With Entecavir to Treat Refractory Liver Fibrosis in Liver Cirrhosis Due to HBV</brief_title>
  <official_title>A Multi-Center Study to Assess the Efficacy and Safety of Traditional Chinese Medicine Combined With Entecavir for Patients With Refractory Liver Fibrosis in Liver Cirrhosis Due to HBV</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ShuGuang Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shanghai Zhongshan Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Guangxi Ruikang Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hubei Hospital of Traditional Chinese Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Huai'an No. 4 People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ruijin Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shenzhen Third People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing Ditan Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing YouAn Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>China-Japan Friendship Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tongji Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wenzhou Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jingmen No.1 People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shandong University of Traditional Chinese Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Ninth Hospital of Nanchang</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The People's Hospital of Ningxia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fifth Hospital of Shijiazhuang City</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Fifth People's Hospital of Suzhou</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Fifth People's Hospital of Anyang</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>ShuGuang Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Liver Cirrhosis is a common pathological consequence of chronic liver disease. Hepatitis B&#xD;
      Virus (HBV) is one of most etiologies of Liver cirrhosis in China. The effective inhibition&#xD;
      of HBV can partially regress or reverse liver fibrosis in patients with chronic Hepatitis and&#xD;
      liver cirrhosis due to HBV, however some patients keep existence or development although HBV&#xD;
      DNA is under-detectable after anti-virals. Theses refractory liver fibrosis is required the&#xD;
      anti-fibrotic treatment focusing on the regulation of hepatic extracellular matrix,&#xD;
      especially is necessary for in the patients with advance fibrosis stage ie. liver cirrhosis.&#xD;
      Fuzheng Huayu has been found to enhance the degradation of collagens in fibrotic liver and&#xD;
      have a good action against liver fibrosis in patients with chronic hepatitis B. However,&#xD;
      there are no high quality clinical evidences which can demonstrate if the combination of&#xD;
      anti-viral and anti-fibrotic therapy can improve the reversion of refractory liver fibrosis&#xD;
      in liver cirrhosis due to HBV.&#xD;
&#xD;
      The primary objective of this study is to establish the safety and efficacy of the&#xD;
      combination of Entecavir and Traditional Chinese Medicine in refractory liver fibrosis in&#xD;
      liver cirrhosis due to HBV.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">June 2019</completion_date>
  <primary_completion_date type="Anticipated">June 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Degree of liver fibrosis</measure>
    <time_frame>48 weeks</time_frame>
    <description>The collagen of liver tissue from 48 week post-treatment patients was stained. 3 pathologists read the slides independently and score the slides with Ishak system. If the Ishak score decrease 1 or more than 1 score, then it is recorded as regression.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">350</enrollment>
  <condition>Hepatitis B Virus Related Cirrhosis</condition>
  <arm_group>
    <arm_group_label>Entecavir+Fuzheng Huayu+TCM Granule</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablet with Entecavir+ Tablet with Fuzheng Huayu+ Granule with TCM</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Entecavir+Fuzheng Huayu+TCM Granule</intervention_name>
    <description>The subjects will be taking 1 Entecavir tablet per day, 4 Fuzheng Huayu tablets three times a day and specific Traditional Chinese Medicine granule for 48 weeks.</description>
    <arm_group_label>Entecavir+Fuzheng Huayu+TCM Granule</arm_group_label>
    <other_name>Gan Ping</other_name>
    <other_name>319 Recipe</other_name>
    <other_name>FZHY</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Hepatitis B history or more than 6 months history of positive HBsAg&#xD;
&#xD;
          -  Within 2 years of Entecavir treatment, HBV-DNA is negative but has not reach the&#xD;
             clinical endpoint (HBeAg seroconversion or HBsAg loss in HBeAg-positive patients;&#xD;
             HBsAg loss or anti-HBs seroconversion in HBeAg-negative patients)&#xD;
&#xD;
          -  Age 18-60&#xD;
&#xD;
          -  Ishak fibrosis score of the biopsy within 6 months ≥5, no anti-fibrosis drug was taken&#xD;
             within 6 months.&#xD;
&#xD;
          -  Child-Pugh&lt;7 (Stage A)&#xD;
&#xD;
          -  The patient or the patient's guardian agrees to participate the random controlled&#xD;
             trial and sign the Informed Consent Form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Decompensated liver cirrhosis&#xD;
&#xD;
          -  HCC&#xD;
&#xD;
          -  Liver histology conforming to other chronic liver diseases, such as moderate or severe&#xD;
             non-alcoholic fatty liver disease(more than 1/3 steatosis in liver ), chronic&#xD;
             hepatitis C, chronic hepatitis D, autoimmune hepatitis, primary biliary cholangitis,&#xD;
             primary sclerosing cholangitis, inherited metabolic liver disease, drug or toxic&#xD;
             induced liver injury, parasitic infections, alcoholic liver disease.&#xD;
&#xD;
          -  Have psychiatric history or uncontrollable epilepsy patient.&#xD;
&#xD;
          -  Uncontrollable diabetic patient&#xD;
&#xD;
          -  History of hemoglobin disease (such as alpha- or beta-thalassemia, sickle cell&#xD;
             disease, spherocytosis) or patients with toxic or autoimmune hemolytic anemia.&#xD;
&#xD;
          -  Severe background disease like chronic respiratory failure, circulatory failure,&#xD;
             kidney failure etc.&#xD;
&#xD;
          -  In situ organ transplantation (such as liver, kidney, lung and heart) or bone marrow&#xD;
             transplantation and stem cell transplantation.&#xD;
&#xD;
          -  Immunocompromised patients: such as HIV infection or take immunosuppressor or&#xD;
             Glucocorticoid (such as cyclosporin, azathioprine, adrenocortical hormone) within 3&#xD;
             months or chemotherapy drugs (such as cyclophosphamide, ammonia and cancer&#xD;
             chemotherapy) and radioactive therapy.&#xD;
&#xD;
          -  Gestation or lactation period women and women who plan to get pregnant during the&#xD;
             study period.&#xD;
&#xD;
          -  Patient who are allergy to the experimental drug.&#xD;
&#xD;
          -  Using history of other anti-viral drug within 6 months.&#xD;
&#xD;
          -  Patients who are participating other trials.&#xD;
&#xD;
          -  Other situation where PI thinks the patient should be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chenghai Liu, PhD</last_name>
    <role>Study Director</role>
    <affiliation>ShuGuang Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chenghai Liu, PhD</last_name>
    <phone>8621-20256521</phone>
    <email>chenghailiu@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Guangxi Ruikang Hospital</name>
      <address>
        <city>Nanning</city>
        <state>Guangxi</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Fifth Hospital of Shijiazhuang</name>
      <address>
        <city>Shijiazhuang</city>
        <state>Hebei</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Fifth People's Hospital of Anyang</name>
      <address>
        <city>Anyang</city>
        <state>Henan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Jingmen No.1 People's Hospital</name>
      <address>
        <city>Jingmen</city>
        <state>Hubei</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hubei Hospital of TCM</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Tongji Hospital</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Huai'an No. 4 People's Hospital</name>
      <address>
        <city>Huai'an</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Fifth People's Hospital of Suzhou</name>
      <address>
        <city>Suzhou</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Ninth Hospital of Nanchang</name>
      <address>
        <city>Nanchang</city>
        <state>Jiangxi</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Ningxia People's Hospital</name>
      <address>
        <city>Yinchuan</city>
        <state>Ningxia</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Affiliated Hospital of Shandong Univercity of TCM</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Wenzhou Central Hospital</name>
      <address>
        <city>Wenzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Beijing Ditan Hospital Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Beijing Youan Hospital Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>China-Japan Friendship Hospital</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>ShuGuang Hospital</name>
      <address>
        <city>Shanghai</city>
        <zip>201203</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhimin Zhao, PhD</last_name>
      <phone>+8615800581663</phone>
      <email>kilorair@sina.com</email>
    </contact>
    <investigator>
      <last_name>Chenghai Liu, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ruijin Hospital</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Shanghai Zhongshan Hospital</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Shenzhen Third People's Hospital</name>
      <address>
        <city>Shenzhen</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>September 12, 2014</study_first_submitted>
  <study_first_submitted_qc>September 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>October 12, 2018</last_update_submitted>
  <last_update_submitted_qc>October 12, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>ShuGuang Hospital</investigator_affiliation>
    <investigator_full_name>Liu Chenghai</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis B</mesh_term>
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Entecavir</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02241616
org study id: SGHLC20140818002
nct id: NCT02241616
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
Liver Cirrhosis is a common pathological consequence of chronic liver disease. Hepatitis B
      Virus (HBV) is one of most etiologies of Liver cirrhosis in China. The effective inhibition
      of HBV can partially regress or reverse liver fibrosis in patients with chronic Hepatitis and
      liver cirrhosis due to HBV, however some patients keep existence or development although HBV
      DNA is under-detectable after anti-virals. Theses refractory liver fibrosis is required the
      anti-fibrotic treatment focusing on the regulation of hepatic extracellular matrix,
      especially is necessary for in the patients with advance fibrosis stage ie. liver cirrhosis.
      Fuzheng Huayu has been found to enhance the degradation of collagens in fibrotic liver and
      have a good action against liver fibrosis in patients with chronic hepatitis B. However,
      there are no high quality clinical evidences which can demonstrate if the combination of
      anti-viral and anti-fibrotic therapy can improve the reversion of refractory liver fibrosis
      in liver cirrhosis due to HBV.

      The primary objective of this study is to establish the safety and efficacy of the
      combination of Entecavir and Traditional Chinese Medicine in refractory liver fibrosis in
      liver cirrhosis due to HBV.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Degree of liver fibrosis
time frame: 48 weeks
description: The collagen of liver tissue from 48 week post-treatment patients was stained. 3 pathologists read the slides independently and score the slides with Ishak system. If the Ishak score decrease 1 or more than 1 score, then it is recorded as regression.
arm group label: Entecavir+Fuzheng Huayu+TCM Granule
arm group type: Experimental
description: Tablet with Entecavir+ Tablet with Fuzheng Huayu+ Granule with TCM
intervention type: Drug
intervention name: Entecavir+Fuzheng Huayu+TCM Granule
description: The subjects will be taking 1 Entecavir tablet per day, 4 Fuzheng Huayu tablets three times a day and specific Traditional Chinese Medicine granule for 48 weeks.
arm group label: Entecavir+Fuzheng Huayu+TCM Granule
other name: Gan Ping
other name: 319 Recipe
other name: FZHY
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Chenghai Liu, PhD
role: Study Director
affiliation: ShuGuang Hospital
last name: Chenghai Liu, PhD
phone: 8621-20256521
email: chenghailiu@hotmail.com
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
country: China
responsible party type: Principal Investigator
investigator affiliation: ShuGuang Hospital
investigator full name: Liu Chenghai
investigator title: Professor
mesh term: Hepatitis B
mesh term: Liver Cirrhosis
mesh term: Fibrosis
mesh term: Entecavir