<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/NCT03042520</url>
  </required_header>
  <id_info>
    <org_study_id>irb20160082</org_study_id>
    <nct_id>NCT03042520</nct_id>
  </id_info>
  <brief_title>Long-term Outcomes of Chronic Hepatitis C Patients Post Sofosbuvir-based Treatment</brief_title>
  <acronym>LONGHEAD</acronym>
  <official_title>Long-term Hepatic and Extra-hepatic Outcomes of Chronic Hepatitis C Patients Post Sofosbuvir-based Interferon-free Treatment (LONGHEAD Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kaohsiung Medical University Chung-Ho Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chang Gung Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cheng-Kung University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chi Mei Medical Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>China Medical University, China</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mackay Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Taipei Veterans General Hospital, Taiwan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Changhua Christian Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pusan National University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Asan Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Korea University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Inje University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Korea University Guro Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kyungpook National University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Seoul National University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Severance Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Samsung Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Seoul National University Bundang Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Soon Chun Hyang University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Seoul St. Mary's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Gachon University Gil Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Dong-A University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Gangnam Severance Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Kaohsiung Medical University Chung-Ho Memorial Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      To evaluate the long-term outcomes including liver related morbidity, mortality and&#xD;
      hepatocellular carcinoma (HCC) development as compared to those of historical control with&#xD;
      interferon(IFN)-based treatment.&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
        1. To access liver fibrosis progression/regression in CHC patients after sofosbuvir-based&#xD;
           treatment.&#xD;
&#xD;
        2. To investigate the long-term outcomes of extrahepatic manifestations of the&#xD;
           sofosbuvir-based treated cohort as compared to their pretreatment status.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Endpoint:&#xD;
&#xD;
      To evaluate the long-term event-free effect after sofosbuvir-based therapy, in terms of free&#xD;
      of major liver events (including HCC, decompensation with ascites, variceal bleeding, hepatic&#xD;
      encephalopathy, and liver-related mortality) in CHC patients.&#xD;
&#xD;
      Secondary Endpoints:&#xD;
&#xD;
        1. To evaluate hepatic fibrosis progression or regression in CHC patients after&#xD;
           sofosbuvir-based therapy.&#xD;
&#xD;
        2. To evaluate the durability of sustained viral response (SVR) in patients achieving SVR&#xD;
           after sofosbuvir-based therapy.&#xD;
&#xD;
        3. To evaluate long-term effect of sofosbuvir-based therapy on the extra-hepatic&#xD;
           manifestations of the cohort. The items include mixed cryoglobulinemia, chronic kidney&#xD;
           diseases, insulin resistance, diabetic status, cardiovascular events and dyslipidemia.&#xD;
&#xD;
        4. To evaluate long-term effect of sofosbuvir-based therapy on quality of life on the&#xD;
           cohort.&#xD;
&#xD;
      Study Design Prospective, longitudinal observational study&#xD;
&#xD;
      Study procedure A total of 200 patients receiving sofosbuvir based direct antiviral agents&#xD;
      (DAAs) in the parent studies will be included for following up to 5 years. Their serological,&#xD;
      image study and disease status description will be prospectively documented to present the&#xD;
      long term effects of sofosbuvir-based therapy.&#xD;
&#xD;
      The presentation of illness will be specified as:&#xD;
&#xD;
        1. Main hepatic complications as liver fibrosis, hepatic malignancy, liver decompensation&#xD;
           with ascites, hepatic encephalopathy and variceal bleeding, and liver-related mortality.&#xD;
&#xD;
        2. Life quality, extrahepatic symptoms as cryoglobulinemia, diabetes mellitus, insulin&#xD;
           resistance, lipid profiles, renal insufficiency and other non-liver morbidities and&#xD;
           malignancy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 2016</start_date>
  <completion_date type="Anticipated">September 2022</completion_date>
  <primary_completion_date type="Anticipated">September 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with liver-related morbidity development during 5-year follow-up period after sofosbuvir-based treatment</measure>
    <time_frame>6 years</time_frame>
    <description>Number of participants with liver-related morbidity during 5-year follow-up period after sofosbuvir-based treatment, including liver fibrosis progression and decompensation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with liver-related mortality development during 5-year follow-up period after sofosbuvir-based treatment</measure>
    <time_frame>6 years</time_frame>
    <description>Number of participants with liver-related mortality assessed by death due to HCC and/or liver decompensation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with hepatocellular carcinoma (HCC) development during 5-year follow-up period after sofosbuvir-based treatment</measure>
    <time_frame>6 years</time_frame>
    <description>Number of participants with HCC assessed by histocytology or positive dynamic image plus alpha fetoprotein (AFP) &gt; 400 ng/ml</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Life quality</measure>
    <time_frame>6 years</time_frame>
    <description>The change of short form(SF)-36 from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cryoglobulinemia</measure>
    <time_frame>6 years</time_frame>
    <description>Change of proportion of participants with cryoglobulinemia from baseline cryoglobulinemia from baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diabetes mellitus (DM)</measure>
    <time_frame>6 years</time_frame>
    <description>Number of participants without DM develop DM assessed by Ac sugar &gt; 126 g/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin resistance</measure>
    <time_frame>6 years</time_frame>
    <description>Change of homeostatic model assessment (HOMA-IR), assessed by Glucose x insulin/22.5 from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid profiles</measure>
    <time_frame>6 years</time_frame>
    <description>Change of the serum profile of lipids including triglyceride(TG), cholesterol(Chol), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal disease</measure>
    <time_frame>6 years</time_frame>
    <description>the change of the estimated glomerular filtration rate (eGFR) from baseline</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Liver Fibroses</condition>
  <condition>HepatoCellular Carcinoma</condition>
  <condition>Cryoglobulinemia</condition>
  <condition>Metabolic Disease</condition>
  <condition>Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>IFN-based therapy historical controls</arm_group_label>
    <description>Patients who had ever participated the parent studies, GS-US-334-0115 or GS-US-337-0131, will be invited to participate the current study in outpatient clinic. For the patients who have participated study will be invited to participate the current study as matched historical control n our outpatient clinic,</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sofosbuvir-based therapy observational group</arm_group_label>
    <description>Patients ≥ 20 of years who had ever participated in parent studies, GS-US-337-0131 (NCT02021656) or GS-US-334-0115 (NCT02021643)&#xD;
Patients who had received at least one dose of sofosbuvir-based therapy in the parent studies.&#xD;
Who IFN-based therapy historical controls, matched with sex, age, level of liver fibrosis and virological response:&#xD;
Patients ≥ 20 of years who had received peginterferon plus ribavirin therapy with match of sex, age, level of liver fibrosis and virological response&#xD;
Patients who have ever participated study will be collected as historical control.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Observation only</intervention_name>
    <arm_group_label>IFN-based therapy historical controls</arm_group_label>
    <arm_group_label>Sofosbuvir-based therapy observational group</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients who had ever participated the parent studies, GS-US-334-0115 or GS-US-337-0131,&#xD;
        will be invited to participate the current study in outpatient clinic. For the patients who&#xD;
        have participated study will be invited to participate the current study as matched&#xD;
        historical control n our outpatient clinic, Written informed consent will be obtained after&#xD;
        full explanation to the patients who had ever participated in parent studies,&#xD;
        GS-US-337-0131 (NCT02021656) or GS-US-334-0115 (NCT02021643) and had received at least one&#xD;
        dose of sofosbuvir-based therapy in the parent studies.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Main inclusion criteria:&#xD;
&#xD;
        For Sofosbuvir-based therapy observational group:&#xD;
&#xD;
          -  Patients ≥ 20 of years who had ever participated in parent studies, GS-US-337-0131&#xD;
             (NCT02021656) or GS-US-334-0115 (NCT02021643)&#xD;
&#xD;
          -  Patients who had received at least one dose of sofosbuvir-based therapy in the parent&#xD;
             studies.&#xD;
&#xD;
        Who IFN-based therapy historical controls, matched with sex, age, level of liver fibrosis&#xD;
        and virological response:&#xD;
&#xD;
          -  Patients ≥ 20 of years who had received pegylated interferon plus ribavirin therapy&#xD;
             with match of sex, age, level of liver fibrosis and virological response&#xD;
&#xD;
          -  Patients who have ever participated study will be collected as historical control.&#xD;
&#xD;
        Main exclusion criteria:&#xD;
&#xD;
          -  Patients not qualified by the main inclusion criteria were excluded.&#xD;
&#xD;
        For Sofosbuvir-based therapy observational group:&#xD;
&#xD;
          -  Patients &lt; 20 of years&#xD;
&#xD;
          -  Patients who are unwilling to participate the current study&#xD;
&#xD;
          -  Patients who had never participated in parent studies, GS-US-337-0131 (NCT02021656)&#xD;
             nor GS-US-334-0115 (NCT02021643)&#xD;
&#xD;
          -  Patients who had never received at least one dose of sofosbuvir-based therapy in the&#xD;
             parent studies.&#xD;
&#xD;
        Who IFN-based therapy historical controls:&#xD;
&#xD;
          -  Patients &lt; 20 of years&#xD;
&#xD;
          -  Patients who are unwilling to participate the current study&#xD;
&#xD;
          -  Patients who had never received pegylated interferon plus ribavirin therapy&#xD;
&#xD;
          -  Patients who did not participate study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ming-Lung Yu</last_name>
    <role>Study Director</role>
    <affiliation>Kaoshiung Medical University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Chia-Yen Dai</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kaoshiung Medical University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jee-Fu Huang</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kaoshiung Medical University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Chung-Feng Huang</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kaoshiung Medical University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ming-Lun Yeh</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kaoshiung Medical University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ching-I Huang</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kaoshiung Medical University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ta-Wei Liu</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kaoshiung Medical University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wan-Long Chuang</last_name>
    <phone>0975-356064</phone>
    <email>waloch@kmu.edu.tw</email>
  </overall_contact>
  <location>
    <facility>
      <name>Korea University Ansan Hospital</name>
      <address>
        <city>Ansan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hyung Joon Yim</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Asan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Young-Suk Lim</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Soon Chun Hyang University Hospital Bucheon.</name>
      <address>
        <city>Bucheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Young Seok Kim</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Dong-A University Hospital</name>
      <address>
        <city>Busan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sang-Young Han</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Inje University Busan Paik Hospital</name>
      <address>
        <city>Busan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Youn-Jae Lee</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Kyungpook National University Hospital</name>
      <address>
        <city>Daegu</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Won Young Tak</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Gachon University Gil Hospital</name>
      <address>
        <city>Incheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ju-Hyun Kim</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Pusan National University Hospital</name>
      <address>
        <city>Pusan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Heo Jeong</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Gangnam Severance Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kwan Sik Lee</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Korea University Guro Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yoon Jun Kim</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Seung Woon Paik</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hosptial</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sook-Hyang Jeong</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kwan Soo Byun</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Seoul St. Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Seung-Kew Yoon</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Severance Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sang Hoon Ahn</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Changhua Christian Hospital</name>
      <address>
        <city>Changhua</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yu-Chun Hsu</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Kaoshiung Medical University Hospital</name>
      <address>
        <city>Kaohsiung City</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wan-Long Chuang</last_name>
      <phone>0975-356064</phone>
      <email>waloch@kmu.edu.tw</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Kaohsiung Chang Gung Memorial Hospital</name>
      <address>
        <city>Kaohsiung</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tsung-Hui Hu</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Keelung Chang Gung Memorial Hospital</name>
      <address>
        <city>Keelung</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rong-Nan Chien</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>China Medical University</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cheng-Yuan Peng</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Chi Mei Liouying Hospital</name>
      <address>
        <city>Tainan</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chih-Chou Chen</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>MacKay Memorial Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Horng-Yuan Wang</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>National Cheng Kung University Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ting-Tsung Chang</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jia-Horng Kao</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chi-Jen Chu</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Linkou Chang Gung Memorial Hospital</name>
      <address>
        <city>Taoyuan</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>I-Shyan Sheen</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
    <country>Taiwan</country>
  </location_countries>
  <removed_countries>
    <country>Korea, Democratic People's Republic of</country>
  </removed_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>December 21, 2016</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>October 10, 2021</last_update_submitted>
  <last_update_submitted_qc>October 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis C, Chronic</mesh_term>
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Cryoglobulinemia</mesh_term>
    <mesh_term>Metabolic Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03042520
org study id: irb20160082
nct id: NCT03042520
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
Primary Objective:

      To evaluate the long-term outcomes including liver related morbidity, mortality and
      hepatocellular carcinoma (HCC) development as compared to those of historical control with
      interferon(IFN)-based treatment.

      Secondary Objective:

        1. To access liver fibrosis progression/regression in CHC patients after sofosbuvir-based
           treatment.

        2. To investigate the long-term outcomes of extrahepatic manifestations of the
           sofosbuvir-based treated cohort as compared to their pretreatment status.
Primary Endpoint:

      To evaluate the long-term event-free effect after sofosbuvir-based therapy, in terms of free
      of major liver events (including HCC, decompensation with ascites, variceal bleeding, hepatic
      encephalopathy, and liver-related mortality) in CHC patients.

      Secondary Endpoints:

        1. To evaluate hepatic fibrosis progression or regression in CHC patients after
           sofosbuvir-based therapy.

        2. To evaluate the durability of sustained viral response (SVR) in patients achieving SVR
           after sofosbuvir-based therapy.

        3. To evaluate long-term effect of sofosbuvir-based therapy on the extra-hepatic
           manifestations of the cohort. The items include mixed cryoglobulinemia, chronic kidney
           diseases, insulin resistance, diabetic status, cardiovascular events and dyslipidemia.

        4. To evaluate long-term effect of sofosbuvir-based therapy on quality of life on the
           cohort.

      Study Design Prospective, longitudinal observational study

      Study procedure A total of 200 patients receiving sofosbuvir based direct antiviral agents
      (DAAs) in the parent studies will be included for following up to 5 years. Their serological,
      image study and disease status description will be prospectively documented to present the
      long term effects of sofosbuvir-based therapy.

      The presentation of illness will be specified as:

        1. Main hepatic complications as liver fibrosis, hepatic malignancy, liver decompensation
           with ascites, hepatic encephalopathy and variceal bleeding, and liver-related mortality.

        2. Life quality, extrahepatic symptoms as cryoglobulinemia, diabetes mellitus, insulin
           resistance, lipid profiles, renal insufficiency and other non-liver morbidities and
           malignancy.
observational model: Cohort
time perspective: Prospective
measure: Number of participants with liver-related morbidity development during 5-year follow-up period after sofosbuvir-based treatment
time frame: 6 years
description: Number of participants with liver-related morbidity during 5-year follow-up period after sofosbuvir-based treatment, including liver fibrosis progression and decompensation
measure: Number of participants with liver-related mortality development during 5-year follow-up period after sofosbuvir-based treatment
time frame: 6 years
description: Number of participants with liver-related mortality assessed by death due to HCC and/or liver decompensation
measure: Number of participants with hepatocellular carcinoma (HCC) development during 5-year follow-up period after sofosbuvir-based treatment
time frame: 6 years
description: Number of participants with HCC assessed by histocytology or positive dynamic image plus alpha fetoprotein (AFP) > 400 ng/ml
measure: Life quality
time frame: 6 years
description: The change of short form(SF)-36 from baseline
measure: Cryoglobulinemia
time frame: 6 years
description: Change of proportion of participants with cryoglobulinemia from baseline cryoglobulinemia from baseline)
measure: Diabetes mellitus (DM)
time frame: 6 years
description: Number of participants without DM develop DM assessed by Ac sugar > 126 g/ml
measure: Insulin resistance
time frame: 6 years
description: Change of homeostatic model assessment (HOMA-IR), assessed by Glucose x insulin/22.5 from baseline
measure: Lipid profiles
time frame: 6 years
description: Change of the serum profile of lipids including triglyceride(TG), cholesterol(Chol), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) from baseline
measure: Renal disease
time frame: 6 years
description: the change of the estimated glomerular filtration rate (eGFR) from baseline
arm group label: IFN-based therapy historical controls
description: Patients who had ever participated the parent studies, GS-US-334-0115 or GS-US-337-0131, will be invited to participate the current study in outpatient clinic. For the patients who have participated study will be invited to participate the current study as matched historical control n our outpatient clinic,
arm group label: Sofosbuvir-based therapy observational group
description: Patients ≥ 20 of years who had ever participated in parent studies, GS-US-337-0131 (NCT02021656) or GS-US-334-0115 (NCT02021643)
Patients who had received at least one dose of sofosbuvir-based therapy in the parent studies.
Who IFN-based therapy historical controls, matched with sex, age, level of liver fibrosis and virological response:
Patients ≥ 20 of years who had received peginterferon plus ribavirin therapy with match of sex, age, level of liver fibrosis and virological response
Patients who have ever participated study will be collected as historical control.
intervention type: Other
intervention name: Observation only
arm group label: IFN-based therapy historical controls
arm group label: Sofosbuvir-based therapy observational group
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Ming-Lung Yu
role: Study Director
affiliation: Kaoshiung Medical University Hospital
last name: Chia-Yen Dai
role: Principal Investigator
affiliation: Kaoshiung Medical University Hospital
last name: Jee-Fu Huang
role: Principal Investigator
affiliation: Kaoshiung Medical University Hospital
last name: Chung-Feng Huang
role: Principal Investigator
affiliation: Kaoshiung Medical University Hospital
last name: Ming-Lun Yeh
role: Principal Investigator
affiliation: Kaoshiung Medical University Hospital
last name: Ching-I Huang
role: Principal Investigator
affiliation: Kaoshiung Medical University Hospital
last name: Ta-Wei Liu
role: Principal Investigator
affiliation: Kaoshiung Medical University Hospital
last name: Wan-Long Chuang
phone: 0975-356064
email: waloch@kmu.edu.tw
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
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: Korea, Republic of
country: Taiwan
country: Korea, Democratic People's Republic of
responsible party type: Sponsor
mesh term: Hepatitis C
mesh term: Hepatitis C, Chronic
mesh term: Liver Cirrhosis
mesh term: Cryoglobulinemia
mesh term: Metabolic Diseases
sharing ipd: No