<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/NCT03778567</url>
  </required_header>
  <id_info>
    <org_study_id>HKUCTR - 1639</org_study_id>
    <nct_id>NCT03778567</nct_id>
  </id_info>
  <brief_title>Renoprotective Effects of Telbivudine in Chronic Hepatitis B</brief_title>
  <official_title>The Effect of Telbivudine on Renal Function in Chronic Hepatitis B Patients With Mild to Moderate Renal Impairment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Hong Kong</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Renal impairment is common in patients with chronic hepatitis B infection. For those taking&#xD;
      nucleotide analogues, renal toxicity of adefovir disoproxil (ADV) and tenofovir disoproxil&#xD;
      fumarate (TDF) is a significant concern in chronic hepatitis B (CHB) patients. Early&#xD;
      observational clinical data suggested that telbivudine (LdT) might have renoprotective&#xD;
      effects. In this prospective study, consecutive CHB patients on combined lamivudine&#xD;
      (LAM)+ADV/TDF are switched to LdT+ADV/TDF at recruitment and are followed up for 24 months.&#xD;
      Estimated glomerular filtration rate (eGFR) is calculated with the Modification of Diet in&#xD;
      Renal Disease (MDRD) equation. The effects of LdT on cell viability and expression of kidney&#xD;
      injury or apoptotic biomarkers are investigated in cultured renal tubular epithelial cell&#xD;
      line HK-2.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background&#xD;
&#xD;
      Both CHB and chronic kidney disease are major health issue affecting millions of persons&#xD;
      worldwide. Based on a large European multicenter database, the Virgil-database, it is&#xD;
      estimated that 15% and 4% of the CHB patients in Europe had mild (GFR 50-80ml/min) and&#xD;
      moderate (GFR &lt;50ml/min) renal impairment respectively . These group of patients require&#xD;
      special attention as the nucleos(t)ides agents (NA) used in the treatment of CHB are cleared&#xD;
      by kidneys and may worsen the kidney function. Recently, a subgroup analysis of the GLOBE&#xD;
      study and 4 small prospective studies provide circumstantial evidence on the use of&#xD;
      telbivudine (LDT) that can improve renal function in CHB patients. However, there are no&#xD;
      prospective, controlled trials to date to evaluate the relationship between LDT and renal&#xD;
      function.&#xD;
&#xD;
      Research plan and methodology&#xD;
&#xD;
      This is a prospective study in CHB patients treated with NA and pre-existing mild to moderate&#xD;
      renal impairment defined as estimated GFR (eGFR) 30-90ml/min.&#xD;
&#xD;
      Aims&#xD;
&#xD;
      To compare the renal function of patients before and after switching lamivudine to&#xD;
      telbivudine.&#xD;
&#xD;
      To determine any adverse events from switching other NA to telbivudine To determine any&#xD;
      biochemical and virological change from switching other NA to telbivudine by checking ALT,&#xD;
      HBV DNA at baseline, and at weeks 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks To determine&#xD;
      any change in 24 hour urinary protein and urinary glucose level To determine the in vitro&#xD;
      effects of telbivudine on renal tubular cells&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2013</start_date>
  <completion_date type="Actual">May 31, 2018</completion_date>
  <primary_completion_date type="Actual">June 16, 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Renal function change</measure>
    <time_frame>108 weeks</time_frame>
    <description>Describe the change in renal function after 108 weeks of telbivudine switch</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Virologic suppression</measure>
    <time_frame>108 weeks</time_frame>
    <description>Rate of virologic suppression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>108 weeks</time_frame>
    <description>Rate of adverse events</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Hepatitis B, Chronic</condition>
  <condition>Chronic Kidney Diseases</condition>
  <arm_group>
    <arm_group_label>lamivudine + nucleotide analogue</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>At the time of recruitment (0 month, baseline), lamivudine is switched to telbivudine while adefovir or tenofovir disoproxil fumarate was continued</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Telbivudine</intervention_name>
    <description>CHB patients who are receiving adefovir or tenofovir disoproxil fumarate are recruited. At the time of recruitment (0 month, baseline), lamivudine is switched to telbivudine while adefovir or tenofovir disoproxil fumarate was continued. The patients are followed-up for 24 months.</description>
    <arm_group_label>lamivudine + nucleotide analogue</arm_group_label>
    <other_name>lamivudine is switched to telbivudine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18 - 70 years&#xD;
&#xD;
          2. Documented HBsAg positivity for at least 6 months. Patients can be either HBeAg&#xD;
             positive AND HBV DNA &lt; 9 log10 copies/mL or HBeAg negative AND HBV DNA &lt; 7 log10&#xD;
             copies/mL&#xD;
&#xD;
          3. On combination therapy (lamivudine and tenofovir or lamivudine and adefovir) for at&#xD;
             least 1 year&#xD;
&#xD;
          4. Documented serum creatinine at least in 2 separate occasions in the last 1 year before&#xD;
             recruitment&#xD;
&#xD;
          5. MDRD eGFR 30-89ml/min at baseline&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Concomitant liver disease including chronic hepatitis C and/or D infection, Wilson's&#xD;
             disease, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing&#xD;
             cholangitis&#xD;
&#xD;
          2. Significant alcohol intake or drug abuse&#xD;
&#xD;
          3. Pregnant subjects&#xD;
&#xD;
          4. Patients with co-existing significant chronic kidney disease (e.g.post renal&#xD;
             transplantation etc.)&#xD;
&#xD;
          5. Allergic to any of the medications involved in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Man-Fung Yuen, DSc, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Hong Kong</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Medicine, The University of Hong Kong, Queen Mary Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 15, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>December 15, 2018</last_update_submitted>
  <last_update_submitted_qc>December 15, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Professor Yuen Man Fung</investigator_full_name>
    <investigator_title>Deputy Head of Department</investigator_title>
  </responsible_party>
  <keyword>chronic hepatitis B infection</keyword>
  <keyword>telbivudine</keyword>
  <keyword>chronic kidney disease</keyword>
  <keyword>nucleotide analogue</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>
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lamivudine</mesh_term>
    <mesh_term>Telbivudine</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/NCT03778567
org study id: HKUCTR - 1639
nct id: NCT03778567
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Renal impairment is common in patients with chronic hepatitis B infection. For those taking
      nucleotide analogues, renal toxicity of adefovir disoproxil (ADV) and tenofovir disoproxil
      fumarate (TDF) is a significant concern in chronic hepatitis B (CHB) patients. Early
      observational clinical data suggested that telbivudine (LdT) might have renoprotective
      effects. In this prospective study, consecutive CHB patients on combined lamivudine
      (LAM)+ADV/TDF are switched to LdT+ADV/TDF at recruitment and are followed up for 24 months.
      Estimated glomerular filtration rate (eGFR) is calculated with the Modification of Diet in
      Renal Disease (MDRD) equation. The effects of LdT on cell viability and expression of kidney
      injury or apoptotic biomarkers are investigated in cultured renal tubular epithelial cell
      line HK-2.
Background

      Both CHB and chronic kidney disease are major health issue affecting millions of persons
      worldwide. Based on a large European multicenter database, the Virgil-database, it is
      estimated that 15% and 4% of the CHB patients in Europe had mild (GFR 50-80ml/min) and
      moderate (GFR <50ml/min) renal impairment respectively . These group of patients require
      special attention as the nucleos(t)ides agents (NA) used in the treatment of CHB are cleared
      by kidneys and may worsen the kidney function. Recently, a subgroup analysis of the GLOBE
      study and 4 small prospective studies provide circumstantial evidence on the use of
      telbivudine (LDT) that can improve renal function in CHB patients. However, there are no
      prospective, controlled trials to date to evaluate the relationship between LDT and renal
      function.

      Research plan and methodology

      This is a prospective study in CHB patients treated with NA and pre-existing mild to moderate
      renal impairment defined as estimated GFR (eGFR) 30-90ml/min.

      Aims

      To compare the renal function of patients before and after switching lamivudine to
      telbivudine.

      To determine any adverse events from switching other NA to telbivudine To determine any
      biochemical and virological change from switching other NA to telbivudine by checking ALT,
      HBV DNA at baseline, and at weeks 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks To determine
      any change in 24 hour urinary protein and urinary glucose level To determine the in vitro
      effects of telbivudine on renal tubular cells
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Renal function change
time frame: 108 weeks
description: Describe the change in renal function after 108 weeks of telbivudine switch
measure: Virologic suppression
time frame: 108 weeks
description: Rate of virologic suppression
measure: Adverse events
time frame: 108 weeks
description: Rate of adverse events
arm group label: lamivudine + nucleotide analogue
arm group type: Other
description: At the time of recruitment (0 month, baseline), lamivudine is switched to telbivudine while adefovir or tenofovir disoproxil fumarate was continued
intervention type: Drug
intervention name: Telbivudine
description: CHB patients who are receiving adefovir or tenofovir disoproxil fumarate are recruited. At the time of recruitment (0 month, baseline), lamivudine is switched to telbivudine while adefovir or tenofovir disoproxil fumarate was continued. The patients are followed-up for 24 months.
arm group label: lamivudine + nucleotide analogue
other name: lamivudine is switched to telbivudine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Man-Fung Yuen, DSc, MD, PhD
role: Principal Investigator
affiliation: The University of Hong Kong
facility: 
country: Hong Kong
responsible party type: Principal Investigator
investigator affiliation: The University of Hong Kong
investigator full name: Professor Yuen Man Fung
investigator title: Deputy Head of Department
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Hepatitis
mesh term: Hepatitis, Chronic
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Lamivudine
mesh term: Telbivudine