<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/NCT03042481</url>
  </required_header>
  <id_info>
    <org_study_id>KMUHIRB-G(I)-20160015</org_study_id>
    <nct_id>NCT03042481</nct_id>
  </id_info>
  <brief_title>Off-therapy Response After Stopping Entecavir or Tenofovir</brief_title>
  <official_title>Comparison and Prediction of Off-therapy Response in Patients of Chronic Hepatitis B Treated With Entecavir or Tenofovir and Achieved Criteria of Stopping Therapy by APASL Guideline</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kaohsiung Medical University Chung-Ho Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kaohsiung Medical University Chung-Ho Memorial Hospital</source>
  <brief_summary>
    <textblock>
      Pegylated-interferon (Peg-IFN) α-2a, entecavir (ETV) and tenofovir disoproxil fumarate (TDF)&#xD;
      are current recommended first-line antiviral therapies for chronic hepatitis B (CHB).&#xD;
      Compared with Peg-IFN therapy, nucleot(s)ide analogue (NUC) therapy has the advantages of&#xD;
      having a potent antiviral effect, and good tolerance without side effect. The long-term&#xD;
      safety and efficacy of ETV and TDF therapy had also been identified. However, poor durability&#xD;
      of the effectiveness after stopping NUC therapy are encountered in the majority of patients.&#xD;
      Previous study identified a high HBV relapse rate of over 50% in HBeAg- positive CHB patients&#xD;
      treated with lamivudine. A recent study investigating the post-treatment durability of ETV&#xD;
      showed that higher to 45.3% of the HBeAg-negative CHB patients happened a clinical relapse&#xD;
      within 1-year after stopping ETV therapy. TDF is another recommended first line NUC with high&#xD;
      potency and high genetic barrier. Although the efficacy of long-term TDF therapy had been&#xD;
      identified, there is lack of data regarding the off-therapy response in CHB patients with TDF&#xD;
      therapy currently. Only a small scale of patients treated with TDF were included in a recent&#xD;
      study investigating off-therapy relapse in non-cirrhotic HBeAg-negative CHB patients after&#xD;
      greater than 4 years of NUC therapy. In addition, the factors associated with off-therapy&#xD;
      response are also still uncertain.&#xD;
&#xD;
      The investigators plan to enrolled 400 CHB patients who had received oral antiviral therapy&#xD;
      ETV or TDF and achieved the Asia Pacific association of the study of liver (APASL) criteria&#xD;
      of stopping NUC therapy. The aims of the study are to investigate the rate of HBV relapse&#xD;
      including virological and clinical relapse in all and between patients with ETV and TDF&#xD;
      therapy, and to identify the predictive factors of relapse.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>April 2016</start_date>
  <completion_date type="Anticipated">May 2021</completion_date>
  <primary_completion_date type="Anticipated">May 2019</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>Rate of HBV relapse</measure>
    <time_frame>One year after stopping HBV antiviral therapy</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate of HBV relapse</measure>
    <time_frame>Two year after stopping HBV antiviral therapy</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of severe hepatitis flare (ALT level ≥10 fold the ULN) with/without hepatic decompensation (total bilirubin ≥2).</measure>
    <time_frame>One year after stopping NUCs</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of severe hepatitis flare (ALT level ≥10 fold the ULN) with/without hepatic decompensation (total bilirubin ≥2).</measure>
    <time_frame>Two year after stopping HBV antiviral therapy</time_frame>
  </secondary_outcome>
  <enrollment type="Anticipated">400</enrollment>
  <condition>Chronic Hepatitis b</condition>
  <eligibility>
    <study_pop>
      <textblock>
        CHB patients who had received oral antiviral therapy ETV or TDF and achieved the Asia&#xD;
        Pacific association of the study of liver (APASL) criteria of stopping nucleot(s)ide&#xD;
        therapy.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female patients &gt;20 years of age&#xD;
&#xD;
          2. Positive HBsAg for more than 6 months prior to ETV or TDF therapy.&#xD;
&#xD;
          3. HBV DNA ≥20,000 IU/mL and alanine aminotransferase (ALT) levels ≥ 2 fold the upper&#xD;
             limit of normal (ULN) for the HBeAg-positive patients, and HBV DNA ≥2000 IU/mL and ALT&#xD;
             levels ≥ 2 fold the ULN for the HBeAg-negative patients prior to ETV or TDF therapy.&#xD;
&#xD;
          4. Achieve the APASL criteria of stopping NUC therapy including HBeAg seroconversion&#xD;
             (negative HBeAg and positive HBeAb) with HBV DNA loss measured at two consecutive&#xD;
             occasions at least 6 months apart for HBeAg positive patients; more than 2 years&#xD;
             therapy with undetectable HBV DNA documented on three separate occasions 6 months&#xD;
             apart for HBeAg negative patients.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hepatitis C virus (HCV) or human immunodeficiency virus (HIV) co-infection.&#xD;
&#xD;
          2. History or other evidence of a medical condition associated with chronic liver disease&#xD;
             other than CHB (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease,&#xD;
             alcoholic liver disease, toxin exposures)&#xD;
&#xD;
          3. Evidence of drug abuse (including excessive alcohol consumption).&#xD;
&#xD;
          4. Prophylactic use of ETV or TDF therapy. (for cancer chemotherapy or post-transplant&#xD;
             immunosuppressive therapy prophylaxis)&#xD;
&#xD;
          5. Patients who have clinical evidence of liver cirrhosis.&#xD;
&#xD;
          6. Inability or unwillingness to provide informed consent or abide by the requirements of&#xD;
             the 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_contact>
    <last_name>MING-LUN YEH, MD</last_name>
    <phone>+886 73121101</phone>
    <phone_ext>7475</phone_ext>
    <email>minglunyeh@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Division of Hepatobiliary, Kaohsiung Medical University Hospital</name>
      <address>
        <city>Kaohsiung</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jee-Fu Huang, Director</last_name>
      <phone>+886 73121101</phone>
      <phone_ext>7475</phone_ext>
      <email>jf71218@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 23, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>February 2, 2017</last_update_submitted>
  <last_update_submitted_qc>February 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 3, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>chronic hepatitis B</keyword>
  <keyword>entecavir</keyword>
  <keyword>tenofovir</keyword>
  <keyword>off-therapy</keyword>
  <keyword>relapse</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis B</mesh_term>
    <mesh_term>Hepatitis B, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Hepatitis, Chronic</mesh_term>
  </condition_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/NCT03042481
org study id: KMUHIRB-G(I)-20160015
nct id: NCT03042481
lead sponsor: 
Pegylated-interferon (Peg-IFN) α-2a, entecavir (ETV) and tenofovir disoproxil fumarate (TDF)
      are current recommended first-line antiviral therapies for chronic hepatitis B (CHB).
      Compared with Peg-IFN therapy, nucleot(s)ide analogue (NUC) therapy has the advantages of
      having a potent antiviral effect, and good tolerance without side effect. The long-term
      safety and efficacy of ETV and TDF therapy had also been identified. However, poor durability
      of the effectiveness after stopping NUC therapy are encountered in the majority of patients.
      Previous study identified a high HBV relapse rate of over 50% in HBeAg- positive CHB patients
      treated with lamivudine. A recent study investigating the post-treatment durability of ETV
      showed that higher to 45.3% of the HBeAg-negative CHB patients happened a clinical relapse
      within 1-year after stopping ETV therapy. TDF is another recommended first line NUC with high
      potency and high genetic barrier. Although the efficacy of long-term TDF therapy had been
      identified, there is lack of data regarding the off-therapy response in CHB patients with TDF
      therapy currently. Only a small scale of patients treated with TDF were included in a recent
      study investigating off-therapy relapse in non-cirrhotic HBeAg-negative CHB patients after
      greater than 4 years of NUC therapy. In addition, the factors associated with off-therapy
      response are also still uncertain.

      The investigators plan to enrolled 400 CHB patients who had received oral antiviral therapy
      ETV or TDF and achieved the Asia Pacific association of the study of liver (APASL) criteria
      of stopping NUC therapy. The aims of the study are to investigate the rate of HBV relapse
      including virological and clinical relapse in all and between patients with ETV and TDF
      therapy, and to identify the predictive factors of relapse.
observational model: Cohort
time perspective: Prospective
measure: Rate of HBV relapse
time frame: One year after stopping HBV antiviral therapy
measure: Rate of HBV relapse
time frame: Two year after stopping HBV antiviral therapy
measure: Rate of severe hepatitis flare (ALT level ≥10 fold the ULN) with/without hepatic decompensation (total bilirubin ≥2).
time frame: One year after stopping NUCs
measure: Rate of severe hepatitis flare (ALT level ≥10 fold the ULN) with/without hepatic decompensation (total bilirubin ≥2).
time frame: Two year after stopping HBV antiviral therapy
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: MING-LUN YEH, MD
phone: +886 73121101
phone ext: 7475
email: minglunyeh@gmail.com
facility: 
status: Recruiting
contact: 
country: Taiwan
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Hepatitis
mesh term: Hepatitis, Chronic