<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/NCT03246048</url>
  </required_header>
  <id_info>
    <org_study_id>PR(AG)136/2017</org_study_id>
    <nct_id>NCT03246048</nct_id>
  </id_info>
  <brief_title>Long Term Follow-up of Hepatitis C Cured Patients</brief_title>
  <official_title>Predicting Outcomes in Hepatitis C Patients With Compensated Advanced Chronic Liver Disease Cured With New Antivirals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Universitari Vall d'Hebron Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Universitari Vall d'Hebron Research Institute</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Objectives:&#xD;
&#xD;
      The general objective of the present project is to gain a better understanding of disease&#xD;
      outcome in cACLD patients treated with the new oral DAA. In particular, the project will&#xD;
      focus on:&#xD;
&#xD;
      - To evaluate the long term prognosis of patients with compensated advanced chronic liver&#xD;
      disease (cACLD) who achieve sustained virological response (SVR) after the new oral&#xD;
      direct-acting antiviral agents (DAA), and determine clinical and elastographic basal and&#xD;
      follow-up parameters to identify low and high risk groups of developing liver-related&#xD;
      decompensation.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      Prospective cohort study in patients with cACLD in whom basal and annual clinical features&#xD;
      and liver stiffness measurements (LSM) will be performed, and survival free of liver-related&#xD;
      events will be analyzed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      HYPOTHESIS:&#xD;
&#xD;
      - The prognosis of cACLD patients who achieve SVR will improve during follow-up and this will&#xD;
      be reflected in an improvement in liver and spleen stiffness and reduction of liver-related&#xD;
      events. However, on an individual basis, because of many confounding factors, predictability&#xD;
      is unknown.&#xD;
&#xD;
      OBJECTIVES:&#xD;
&#xD;
      The general objective of the present project is to gain a better understanding of disease&#xD;
      outcome in cACLD patients treated with the new oral DAA. In particular, the project will&#xD;
      focus on to determine simple clinical and elastographic basal and follow-up parameters to&#xD;
      identify low and high risk groups for developing liver-related decompensation in cACLD&#xD;
      patients who achieve SVR after DAA therapy. As a consequence of this, to provide guidance to&#xD;
      clinicians to decide which cACLD patients should be indefinitely followed and which ones can&#xD;
      be discharged from follow up, and also provide solid information to patients regarding the&#xD;
      possible outcome of their cACLD after SVR.&#xD;
&#xD;
        -  Study design: Prospective cohort study in an academic center to evaluate long term&#xD;
           prognosis of patients with cACLD who achieve SVR after DAA therapy.&#xD;
&#xD;
        -  Research subjects: All consecutive patients meeting inclusion criteria who have received&#xD;
           DAA therapy from 1st January 2015 to 31st March 2016.&#xD;
&#xD;
        -  Variables: Variables will be collected at baseline and annually for a period of 5 years.&#xD;
           Basal data on genotype/subtype, interleukin 28B, viremia, type and duration of therapy.&#xD;
           Data of liver function (INR, albumin, bilirubin), platelet count, aspartate&#xD;
           aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP),&#xD;
           gamma-glutamyltransferase (GGT), US findings (spleen size, collaterals), liver and&#xD;
           spleen stiffness, body mass index (BMI), presence of metabolic syndrome factors&#xD;
           (diabetes, dyslipemia, hypertension), alcohol and tabacco use, treatment with statins&#xD;
           and development of liver-related events. The subgroup of patients with known esophageal&#xD;
           varices prior to therapy will receive a second endoscopy 12-18 months after finishing&#xD;
           therapy. Liver biopsies will be performed (after consent) at the end of follow-up (5&#xD;
           years) in the group of patients who will be candidates for being discharged (LSM&lt;10 kPa)&#xD;
           to ensure cirrhosis regression and learn about the correlation between LSM and histology&#xD;
           after SVR.&#xD;
&#xD;
        -  Data collection methods and analysis: Patients will be monitored at the outpatient&#xD;
           clinics every 6 months as per usual clinical practice. Every 6 months, clinical data,&#xD;
           laboratory tests and abdominal US will be obtained. Liver and spleen stiffness&#xD;
           (Fibroscan, Echosens) will be performed annually after finishing treatment by an&#xD;
           experienced member (MP), using usual quality criteria. Spleen stiffness measurements&#xD;
           will be performed under US spleen localization and with the same device and conditions&#xD;
           than liver stiffness. All data will be registered in a database.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2016</start_date>
  <completion_date type="Actual">June 2021</completion_date>
  <primary_completion_date type="Actual">January 2021</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>Incidence of liver decompensation and/or death and hepatocellular carcinoma</measure>
    <time_frame>5 years</time_frame>
    <description>Incidence of liver related events (decompensation and hepatocellular carcinoma) during follow-up</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlate values of liver stiffness with histology changes at the end of follow up</measure>
    <time_frame>5 years</time_frame>
    <description>Correlate liver fibrosis in liver biopsy with liver stiffness cut-offs.</description>
  </secondary_outcome>
  <enrollment type="Actual">300</enrollment>
  <condition>Chronic Hepatitis C</condition>
  <condition>Chronic Liver Disease</condition>
  <condition>Cirrhosis</condition>
  <eligibility>
    <study_pop>
      <textblock>
        All consecutive patients meeting inclusion criteria who have received DAA therapy from 1st&#xD;
        January 2015 to 31st March 2016.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients having suggestive or highly suggestive cACLD defined as LSM 10-15 kPa or LSM&#xD;
             ≥15 kPa, respectively. Patients with suggestive cACLD (LSM 10-15 kPa) will be divided&#xD;
             in two subgroups depending on the presence of at least one of the following:&#xD;
             gastroesophageal varices, hepatic venous pressure gradient (HVPG) &gt;5 mmHg, nodular&#xD;
             liver or collateral circulation in US, splenomegaly (&gt;=13 cm) or platelet count&#xD;
             &lt;150,000. Patients with suggestive cACLD (LSM 10-15 kPa) and none of the prior&#xD;
             characteristics will form the subgroup of occult cACLD.&#xD;
&#xD;
          2. Age between 18-85 years old.&#xD;
&#xD;
          3. SVR after antiviral therapy.&#xD;
&#xD;
          4. Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of liver decompensation.&#xD;
&#xD;
          2. Hepatitis B virus coinfection.&#xD;
&#xD;
          3. HIV infection.&#xD;
&#xD;
          4. Prior liver transplantation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joan Genescà</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Vall d'Hebron</affiliation>
  </overall_official>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>September 19, 2022</last_update_submitted>
  <last_update_submitted_qc>September 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 21, 2022</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 A</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis C, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Liver Diseases</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/NCT03246048
org study id: PR(AG)136/2017
nct id: NCT03246048
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Objectives:

      The general objective of the present project is to gain a better understanding of disease
      outcome in cACLD patients treated with the new oral DAA. In particular, the project will
      focus on:

      - To evaluate the long term prognosis of patients with compensated advanced chronic liver
      disease (cACLD) who achieve sustained virological response (SVR) after the new oral
      direct-acting antiviral agents (DAA), and determine clinical and elastographic basal and
      follow-up parameters to identify low and high risk groups of developing liver-related
      decompensation.

      Methods:

      Prospective cohort study in patients with cACLD in whom basal and annual clinical features
      and liver stiffness measurements (LSM) will be performed, and survival free of liver-related
      events will be analyzed.
HYPOTHESIS:

      - The prognosis of cACLD patients who achieve SVR will improve during follow-up and this will
      be reflected in an improvement in liver and spleen stiffness and reduction of liver-related
      events. However, on an individual basis, because of many confounding factors, predictability
      is unknown.

      OBJECTIVES:

      The general objective of the present project is to gain a better understanding of disease
      outcome in cACLD patients treated with the new oral DAA. In particular, the project will
      focus on to determine simple clinical and elastographic basal and follow-up parameters to
      identify low and high risk groups for developing liver-related decompensation in cACLD
      patients who achieve SVR after DAA therapy. As a consequence of this, to provide guidance to
      clinicians to decide which cACLD patients should be indefinitely followed and which ones can
      be discharged from follow up, and also provide solid information to patients regarding the
      possible outcome of their cACLD after SVR.

        -  Study design: Prospective cohort study in an academic center to evaluate long term
           prognosis of patients with cACLD who achieve SVR after DAA therapy.

        -  Research subjects: All consecutive patients meeting inclusion criteria who have received
           DAA therapy from 1st January 2015 to 31st March 2016.

        -  Variables: Variables will be collected at baseline and annually for a period of 5 years.
           Basal data on genotype/subtype, interleukin 28B, viremia, type and duration of therapy.
           Data of liver function (INR, albumin, bilirubin), platelet count, aspartate
           aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP),
           gamma-glutamyltransferase (GGT), US findings (spleen size, collaterals), liver and
           spleen stiffness, body mass index (BMI), presence of metabolic syndrome factors
           (diabetes, dyslipemia, hypertension), alcohol and tabacco use, treatment with statins
           and development of liver-related events. The subgroup of patients with known esophageal
           varices prior to therapy will receive a second endoscopy 12-18 months after finishing
           therapy. Liver biopsies will be performed (after consent) at the end of follow-up (5
           years) in the group of patients who will be candidates for being discharged (LSM<10 kPa)
           to ensure cirrhosis regression and learn about the correlation between LSM and histology
           after SVR.

        -  Data collection methods and analysis: Patients will be monitored at the outpatient
           clinics every 6 months as per usual clinical practice. Every 6 months, clinical data,
           laboratory tests and abdominal US will be obtained. Liver and spleen stiffness
           (Fibroscan, Echosens) will be performed annually after finishing treatment by an
           experienced member (MP), using usual quality criteria. Spleen stiffness measurements
           will be performed under US spleen localization and with the same device and conditions
           than liver stiffness. All data will be registered in a database.
observational model: Cohort
time perspective: Prospective
measure: Incidence of liver decompensation and/or death and hepatocellular carcinoma
time frame: 5 years
description: Incidence of liver related events (decompensation and hepatocellular carcinoma) during follow-up
measure: Correlate values of liver stiffness with histology changes at the end of follow up
time frame: 5 years
description: Correlate liver fibrosis in liver biopsy with liver stiffness cut-offs.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Joan Genescà
role: Principal Investigator
affiliation: Hospital Vall d'Hebron
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis C, Chronic
mesh term: Hepatitis
mesh term: Liver Diseases