<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/NCT01711567</url>
  </required_header>
  <id_info>
    <org_study_id>STEEP study</org_study_id>
    <nct_id>NCT01711567</nct_id>
  </id_info>
  <brief_title>Tenofovir Disoproxil Fumarate vs. Entecavir in Chronic Hepatitis B Patients With Partial Virologic Response to Entecavir</brief_title>
  <acronym>STEEP</acronym>
  <official_title>Switching to Tenofovir Disoproxil Fumarate vs. Continuing Entecavir in Chronic Hepatitis B Patients With Partial Virologic Response During Entecavir Therapy: STEEP Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Korea University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Korea University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Entecavir, a potent antiviral agent, has been widely used for treatment-naïve chronic&#xD;
      hepatitis B patients. However, about 20% of patients showed partial virologic response after&#xD;
      2 year of entecavir therapy (33% in HBeAg positive, 10% in HBeAg negative patients).&#xD;
      Tenofovir is a nucleotide analogue with more potent antiviral activity. In addition, there is&#xD;
      no cross resistance between the two drugs. Therefore it is assumed that tenofovir would be&#xD;
      effective in the treatment of chronic hepatitis B patients who shows partial virologic&#xD;
      response (detectable HBV DNA by real time PCR after 12 months of treatment) despite treatment&#xD;
      with entecavir. In this study, we will compare the efficacy of switching to tenofovir with&#xD;
      continuing entecavir in patients who shows partial virologic response to entecavir.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The number of patients needed was calculated using PASS 2008. We hypothesized that two-thirds&#xD;
      (65%) of the patients receiving TDF, and one-fifth (20%) of the patients receiving ETV, would&#xD;
      achieve virologic response. We also assumed a 15% drop-out rate; thus, 22 patients were&#xD;
      needed in each group to achieve 80% power to demonstrate a difference between the groups with&#xD;
      a 5% level of significance.&#xD;
&#xD;
      The primary efficacy end point will be analyzed on a per-protocol basis, including only those&#xD;
      patients who had completed the treatment schedule of study. In contrast, the&#xD;
      intention-to-treat analysis will include all randomized subjects, even those dropped-out from&#xD;
      the study before 12 months, as cases of treatment failure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2013</start_date>
  <completion_date type="Actual">November 2016</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Virologic response rate at year 1 (12 months) (HBV DNA &lt; 20 IU/mL)</measure>
    <time_frame>up to the end of year 1 (12 months)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>-Degree of HBV DNA reduction, mean HBV DNA, biochemical and serologic response rates, resistance, and adverse events at year 1</measure>
    <time_frame>up to the end of year 1 (12 months)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Chronic Hepatitis B</condition>
  <arm_group>
    <arm_group_label>entecavir</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>standard drugs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>tenofovir</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>study drugs</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>tenofovir</intervention_name>
    <description>tenofovir 300 mg qd</description>
    <arm_group_label>tenofovir</arm_group_label>
    <other_name>tenofovir (viread)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>entecavir</intervention_name>
    <description>entecavir 0.5 mg qd</description>
    <arm_group_label>entecavir</arm_group_label>
    <other_name>entecavir(baraclude) 0.5 mg qd</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. CHB patients (positive HBsAg more than 6 months)&#xD;
&#xD;
          2. Age 19 years old&#xD;
&#xD;
          3. HBeAg positive or negative patients&#xD;
&#xD;
          4. Patients receiving entecavir 0.5 mg more than 12 months&#xD;
&#xD;
          5. Detectable HBV DNA by real time PCR (HBV &gt; 60 IU/mL)&#xD;
&#xD;
          6. Compensated liver function (Child-Pugh-Turcotte score ≤7, prothrombin time 3 sec above&#xD;
             ULN or INR ≤1.5, serum albumin &gt;3 g/dL, total bilirubin &lt;2.5 mg/dL, no history of&#xD;
             variceal bleeding, diuretics or ascites requiring paracentesis, hepatic&#xD;
             encephalopathy)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of treatment with nucleotide analogue other than 0.5 mg of ETV&#xD;
&#xD;
          2. Serum creatinine level &gt; 1.5 mg/dL or creatinine clearance &lt; 50 mL/min&#xD;
&#xD;
          3. Absolute neutrophil count ≤ 1000 cell/mL&#xD;
&#xD;
          4. Hemoglobin level ≤ 10 g/dL in men or ≤ 9 g/dL in women&#xD;
&#xD;
          5. Antiviral resistance mutations on rtT184, rtS202, or rtM250 + rtM204V/I&#xD;
&#xD;
          6. A positive antibody test for human immunodeficiency virus, hepatitis C virus, or&#xD;
             hepatitis D virus&#xD;
&#xD;
          7. Pregnancy or lactation&#xD;
&#xD;
          8. HCC (in cases where alfa-fetoprotein levels were over 100 ng/mL, abdominal computed&#xD;
             tomography or magnetic resonance image was performed to exclude HCC)&#xD;
&#xD;
          9. Untreated malignancy other than HCC.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hyung Joon Yim, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Korea University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Korea University Ansan Hospital</name>
      <address>
        <city>Ansan</city>
        <state>Gyeonggi-do</state>
        <zip>425-707</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>October 17, 2012</study_first_submitted>
  <study_first_submitted_qc>October 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 22, 2012</study_first_posted>
  <last_update_submitted>November 8, 2016</last_update_submitted>
  <last_update_submitted_qc>November 8, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 9, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Korea University</investigator_affiliation>
    <investigator_full_name>Hyung Joon Yim</investigator_full_name>
    <investigator_title>Associate professor</investigator_title>
  </responsible_party>
  <keyword>Chronic Hepatitis B</keyword>
  <keyword>TENOFOVIR</keyword>
  <keyword>ENTECAVIR</keyword>
  <keyword>PARTIAL RESPONDER</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
    <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/NCT01711567
org study id: STEEP study
nct id: NCT01711567
lead sponsor: 
collaborator: 
has dmc: Yes
Entecavir, a potent antiviral agent, has been widely used for treatment-naïve chronic
      hepatitis B patients. However, about 20% of patients showed partial virologic response after
      2 year of entecavir therapy (33% in HBeAg positive, 10% in HBeAg negative patients).
      Tenofovir is a nucleotide analogue with more potent antiviral activity. In addition, there is
      no cross resistance between the two drugs. Therefore it is assumed that tenofovir would be
      effective in the treatment of chronic hepatitis B patients who shows partial virologic
      response (detectable HBV DNA by real time PCR after 12 months of treatment) despite treatment
      with entecavir. In this study, we will compare the efficacy of switching to tenofovir with
      continuing entecavir in patients who shows partial virologic response to entecavir.
The number of patients needed was calculated using PASS 2008. We hypothesized that two-thirds
      (65%) of the patients receiving TDF, and one-fifth (20%) of the patients receiving ETV, would
      achieve virologic response. We also assumed a 15% drop-out rate; thus, 22 patients were
      needed in each group to achieve 80% power to demonstrate a difference between the groups with
      a 5% level of significance.

      The primary efficacy end point will be analyzed on a per-protocol basis, including only those
      patients who had completed the treatment schedule of study. In contrast, the
      intention-to-treat analysis will include all randomized subjects, even those dropped-out from
      the study before 12 months, as cases of treatment failure.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Virologic response rate at year 1 (12 months) (HBV DNA < 20 IU/mL)
time frame: up to the end of year 1 (12 months)
measure: -Degree of HBV DNA reduction, mean HBV DNA, biochemical and serologic response rates, resistance, and adverse events at year 1
time frame: up to the end of year 1 (12 months)
arm group label: entecavir
arm group type: Active Comparator
description: standard drugs
arm group label: tenofovir
arm group type: Active Comparator
description: study drugs
intervention type: Drug
intervention name: tenofovir
description: tenofovir 300 mg qd
arm group label: tenofovir
other name: tenofovir (viread)
intervention type: Drug
intervention name: entecavir
description: entecavir 0.5 mg qd
arm group label: entecavir
other name: entecavir(baraclude) 0.5 mg qd
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Hyung Joon Yim, M.D.
role: Principal Investigator
affiliation: Korea University
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Korea University
investigator full name: Hyung Joon Yim
investigator title: Associate professor
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Hepatitis
mesh term: Hepatitis, Chronic
mesh term: Tenofovir
mesh term: Entecavir