<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/NCT03248622</url>
  </required_header>
  <id_info>
    <org_study_id>999917099</org_study_id>
    <secondary_id>17-DK-N099</secondary_id>
    <nct_id>NCT03248622</nct_id>
  </id_info>
  <brief_title>Hepatitis B Reactivation During Treatment With Direct-Acting Antiviral Agents for Chronic Hepatitis C Infection</brief_title>
  <official_title>Hepatitis B Reactivation During Treatment With Direct-Acting Antiviral Agents for Chronic Hepatitis C Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Treatment of some diseases can suppress the immune system. This can cause other conditions to&#xD;
      reactivate. Recent cases have shown that hepatitis B virus (HBV) reactivates in people who&#xD;
      had already recovered from it during treatment for chronic hepatitis C (CHC). Their treatment&#xD;
      was direct-acting antiviral (DAA) agents. Researchers want to see how common this&#xD;
      reactivation is. They want to learn what the effects are. They will study data that have&#xD;
      already been collected.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      To study HBV reactivation in people with CHC and resolved HBV infection who are being treated&#xD;
      with interferon-free DAA-based therapy.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Data were collected from adults 18 and older in studies that were done in 2012 and 2016.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Researchers will screen the records from the previous studies. They will identify&#xD;
      participants who had HBV infection before they got DAA-based treatment.&#xD;
&#xD;
      Researchers will take data from those records. This will include data on:&#xD;
&#xD;
        -  Age, sex, race, and ethnicity&#xD;
&#xD;
        -  Treatment and disease status&#xD;
&#xD;
        -  Lab results&#xD;
&#xD;
      Researchers will test stored samples. They will test samples that were taken before, during,&#xD;
      and after treatment. They will check if HBV was reactivated. They will also check if other&#xD;
      clinical outcomes occurred.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Reactivation of hepatitis B is well known to occur with immunosuppression as in the setting&#xD;
      of high dose immunosuppressive therapy, cancer chemotherapy and bone marrow or stem cell&#xD;
      transplantation. It is usually subclinical but at times can manifest as an acute hepatitis,&#xD;
      hepatic decompensation and death. Often times this leads to interruption of cancer&#xD;
      chemotherapy.&#xD;
&#xD;
      Recently, several case reports and case series have revealed evidence of hepatitis B virus&#xD;
      (HBV) reactivation in previously recovered persons being treated for chronic hepatitis C&#xD;
      (CHC) with direct-acting antiviral (DAA) agents. Given the severity of some cases, the U.S.&#xD;
      Food and Drug Administration (FDA) has issued a Black Box warning regarding the risk of HBV&#xD;
      reactivation to HCV DAA labeling to screen all hepatitis C patients for HBV before initiation&#xD;
      of therapy and to monitor those with previous HBV infection for signs of reactivation while&#xD;
      on treatment. However, since the FDA warning, retrospective experiences on clinical trials&#xD;
      have failed to reveal evidence of viral reactivation. Further, the frequency of HBV&#xD;
      reactivation and its risk factors and monitoring frequency in HCV patients receiving&#xD;
      Interferon-free DAA therapy are yet unknown. Hence, we aim to conduct a multicenter&#xD;
      retrospective analysis to investigate these issues.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 3, 2017</start_date>
  <completion_date type="Actual">May 28, 2019</completion_date>
  <primary_completion_date type="Actual">May 28, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The rate of HBV reactivation among patient with resolved HBV infection undergoing Interferon-free DAA-based therapy for HCV infection.</measure>
    <time_frame>From initiation of treatment to 24 weeks post-treatment</time_frame>
    <description>Detection of HBV DNA or HBsAg and elevated ALT level</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">79</enrollment>
  <condition>Hepatitis B</condition>
  <arm_group>
    <arm_group_label>Anti-HBc positive</arm_group_label>
    <description>Anti-HBc positive</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HCV positive Cohort</arm_group_label>
    <description>HCV positive Cohort</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with hepatitis C who were anti-HBc positive and who received treatment with a&#xD;
        direct acting antiviral agent.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Adult patients (greater than or equal to 18 years) with CHC who underwent treatment&#xD;
             with an Interferon-free DAA-based therapy.&#xD;
&#xD;
          -  Evidence of resolved HBV infection prior to starting interferon-free DAAbased therapy&#xD;
             (HBsAg-negative with positive anti-HBc +/- positive anti-HBs)&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        - Treatment with Nucleos(t)ide Analogues (NA) active against HBV prior to initiation of&#xD;
        interferon-free DAA therapy&#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_official>
    <last_name>Marc G Ghany, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institute of Diabetes and Digestive and Kidney Disorders (NIDDK)</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <last_update_submitted>May 29, 2019</last_update_submitted>
  <last_update_submitted_qc>May 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 30, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Incidence</keyword>
  <keyword>Hepatitis B Surface Antigen</keyword>
  <keyword>Decompensation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis B</mesh_term>
    <mesh_term>Hepatitis C, Chronic</mesh_term>
    <mesh_term>Hepatitis</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/NCT03248622
org study id: 999917099
secondary id: 17-DK-N099
nct id: NCT03248622
lead sponsor: 
Background:

      Treatment of some diseases can suppress the immune system. This can cause other conditions to
      reactivate. Recent cases have shown that hepatitis B virus (HBV) reactivates in people who
      had already recovered from it during treatment for chronic hepatitis C (CHC). Their treatment
      was direct-acting antiviral (DAA) agents. Researchers want to see how common this
      reactivation is. They want to learn what the effects are. They will study data that have
      already been collected.

      Objectives:

      To study HBV reactivation in people with CHC and resolved HBV infection who are being treated
      with interferon-free DAA-based therapy.

      Eligibility:

      Data were collected from adults 18 and older in studies that were done in 2012 and 2016.

      Design:

      Researchers will screen the records from the previous studies. They will identify
      participants who had HBV infection before they got DAA-based treatment.

      Researchers will take data from those records. This will include data on:

        -  Age, sex, race, and ethnicity

        -  Treatment and disease status

        -  Lab results

      Researchers will test stored samples. They will test samples that were taken before, during,
      and after treatment. They will check if HBV was reactivated. They will also check if other
      clinical outcomes occurred.
Reactivation of hepatitis B is well known to occur with immunosuppression as in the setting
      of high dose immunosuppressive therapy, cancer chemotherapy and bone marrow or stem cell
      transplantation. It is usually subclinical but at times can manifest as an acute hepatitis,
      hepatic decompensation and death. Often times this leads to interruption of cancer
      chemotherapy.

      Recently, several case reports and case series have revealed evidence of hepatitis B virus
      (HBV) reactivation in previously recovered persons being treated for chronic hepatitis C
      (CHC) with direct-acting antiviral (DAA) agents. Given the severity of some cases, the U.S.
      Food and Drug Administration (FDA) has issued a Black Box warning regarding the risk of HBV
      reactivation to HCV DAA labeling to screen all hepatitis C patients for HBV before initiation
      of therapy and to monitor those with previous HBV infection for signs of reactivation while
      on treatment. However, since the FDA warning, retrospective experiences on clinical trials
      have failed to reveal evidence of viral reactivation. Further, the frequency of HBV
      reactivation and its risk factors and monitoring frequency in HCV patients receiving
      Interferon-free DAA therapy are yet unknown. Hence, we aim to conduct a multicenter
      retrospective analysis to investigate these issues.
observational model: Case-Only
time perspective: Retrospective
measure: The rate of HBV reactivation among patient with resolved HBV infection undergoing Interferon-free DAA-based therapy for HCV infection.
time frame: From initiation of treatment to 24 weeks post-treatment
description: Detection of HBV DNA or HBsAg and elevated ALT level
arm group label: Anti-HBc positive
description: Anti-HBc positive
arm group label: HCV positive Cohort
description: HCV positive Cohort
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marc G Ghany, M.D.
role: Principal Investigator
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis B
mesh term: Hepatitis C, Chronic
mesh term: Hepatitis