<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/NCT03775798</url>
  </required_header>
  <id_info>
    <org_study_id>17-062</org_study_id>
    <nct_id>NCT03775798</nct_id>
  </id_info>
  <brief_title>Incidence of de Novo Hepatocellular Carcinoma After Antiviral Agents for HCV.</brief_title>
  <official_title>Incidence of de Novo Hepatocellular Carcinoma After Direct-acting Antiviral Agents for HCV: a Multicenter Prospective Cohort Study From Latin America.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Austral University, Argentina</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Austral University, Argentina</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main risk factor for development of hepatocellular carcinoma (HCC) is cirrhosis of any&#xD;
      etiology, with an annual incidence risk between 1-6%; currently the leading cause of death in&#xD;
      patients with cirrhosis and the 2nd cause of death by cancer worldwide. Chronic hepatitis C&#xD;
      (HCV) is the first single cause associated to cirrhosis and HCC in the Western world.&#xD;
&#xD;
      With the advent of new direct antiviral agents (DAA) of chronic HCV infection, virological&#xD;
      cure generally exceeds 90% of the cases. Previous studies have shown that the incidence of&#xD;
      HCC is lower in patients with virologic cure after treatment with pegINF schemes. However,&#xD;
      recently published data, open up more controversy regarding the incidence of HCC after&#xD;
      virologic cure with DAA. An increasing incidence of HCC after virologic cure in patients&#xD;
      treated with DAA has been observed, opening a paradox yet unexplained.&#xD;
&#xD;
      This project proposes to answer the following clinical research question: in patients with&#xD;
      HCV cirrhosis treated with DAA, is there a change in the incidence of hepatocellular&#xD;
      carcinoma? To answer this question a prospective longitudinal cohort study of patients with&#xD;
      Child Pugh A-B cirrhosis will be held at 3 years minimum follow-up.&#xD;
&#xD;
      A minimum of 210 patients will be included with clinical or histological or non-invasive&#xD;
      diagnosis of cirrhosis Child Pugh A or B, with HCV treated with DAA and without&#xD;
      hepatocellular carcinoma at the time of enrollment. From this cohort, patients who develop&#xD;
      HCC during follow-up will be identified. Routine screening will be done through ultrasound&#xD;
      every 6 months in all subjects enrolled and the diagnosis of HCC will be according to&#xD;
      recommendations of European and American guidelines.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Name of the study:&#xD;
&#xD;
      INCIDENCE OF HEPATOCELLULAR CARCINOMA IN CIRRHOTIC PATIENTS WITH HEPATITIS C INFECTION,&#xD;
      TRETAED WITH DIRECT ANTIVIRAL AGENTS IN LATIN AMERICA: A MULTICENTER PROSPECTIVE COHORT STUDY&#xD;
&#xD;
      With the advent of new direct antiviral agents (DAA) of chronic HCV infection, virological&#xD;
      cure generally exceeds 90% of the cases. Previous studies have shown that the incidence of&#xD;
      HCC is lower in patients with virologic cure after treatment with pegINF schemes. However,&#xD;
      recently published data, open up more controversy regarding the incidence of HCC after&#xD;
      virologic cure with DAA. An increasing incidence of HCC after virologic cure in patients&#xD;
      treated with DAA has been observed, opening a paradox yet unexplained.&#xD;
&#xD;
      This project proposes to answer the following clinical research question: in patients with&#xD;
      HCV cirrhosis treated with DAA, is there a change in the incidence of hepatocellular&#xD;
      carcinoma? To answer this question a prospective longitudinal cohort study of patients with&#xD;
      Child Pugh A-B cirrhosis will be held at 3 years minimum follow-up.&#xD;
&#xD;
      A minimum of 210 patients will be included with clinical or histological or non-invasive&#xD;
      diagnosis of cirrhosis Child Pugh A or B, with HCV treated with DAA and without&#xD;
      hepatocellular carcinoma at the time of enrollement. From this cohort, patients who develop&#xD;
      HCC during follow-up will be identified. Routine screening will be done through ultrasound&#xD;
      every 6 months in all subjects enrolled and the diagnosis of HCC will be according to&#xD;
      recommendations of European and American guidelines.&#xD;
&#xD;
      However, preliminary results presented at the last European Congress of Hepatology in&#xD;
      Barcelona, Spain, and early published in Journal of Heaptology, open up more controversy&#xD;
      regarding the incidence of HCC after virologic cure post DAA. An unexpected higher incidence&#xD;
      and recurrence of HCC after treatment with these new drugs has been observed, opening a&#xD;
      paradox yet unexplained. Of particular interest then, is to clarify and find if there is a&#xD;
      change in the incidence of HCC in HCV cirrhosis after treatment with DAA in our region. It is&#xD;
      relevant on the other hand; that this study would be the first longitudinal cohort study&#xD;
      evaluating the development of HCC in patients with cirrhosis in Latin America. It is then&#xD;
      expected that the results would be extremely important to the medical science from this&#xD;
      region.&#xD;
&#xD;
      Clinical Research Question In patients with HCV cirrhosis treated DAA, is there a change in&#xD;
      the incidence of hepatocellular carcinoma? Primary Objective To evaluate the incidence of HCC&#xD;
      after treatment with DAA in patients with Child Pugh A or B cirrhosis and chronic HCV&#xD;
      infection.&#xD;
&#xD;
      Secondary Objectives&#xD;
&#xD;
      Secondary objectives will be related to:&#xD;
&#xD;
        -  Incidence of HCC between cured and uncured of HCV with DAA.&#xD;
&#xD;
        -  Impact of routine screening on survival in patients with HCC.&#xD;
&#xD;
        -  Risk factors for development of hepatocellular carcinoma in patients with HCV treated&#xD;
           with DAA.&#xD;
&#xD;
        -  Adverse events and incidence of cirrhosis decompensation after DAA.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 1, 2016</start_date>
  <completion_date type="Anticipated">January 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2020</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>36 Months</target_duration>
  <primary_outcome>
    <measure>Incidence of hepatocellular carcinoma after direct-acting antivirals for HCV</measure>
    <time_frame>Three year period</time_frame>
    <description>Cumulative incidence, Hazard ratios (95% CI)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of direct-acting antivirals for HCV</measure>
    <time_frame>Three year period</time_frame>
    <description>Achievement of RVS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events after direct-acting antivirals for HCV</measure>
    <time_frame>Three year period</time_frame>
    <description>Safety</description>
  </secondary_outcome>
  <enrollment type="Anticipated">2200</enrollment>
  <condition>Hepatitis C</condition>
  <condition>Cirrhosis</condition>
  <condition>Antiviral Drug Adverse Reaction</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Direct antiviral agents for hepatitis C</intervention_name>
    <description>Direct-acting antivirals for hepatitis C</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        A consecutive non-probability sampling of subjects with clinical, histological or&#xD;
        non-invasive diagnosis of cirrhosis, functional status Child Pugh class A or B with chronic&#xD;
        HCV infection treated with DAA will be made. On a cohort of patients with these&#xD;
        characteristics that meet the following eligibility criteria, a minimum 3-year follow-up&#xD;
        will be done.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed Informed Consent (CI) obtained prior to any study specific procedure. Patients&#xD;
             should be able to understand written informed and be ready to sign it (ANNEX I).&#xD;
&#xD;
          -  Men and women 18 years or older.&#xD;
&#xD;
          -  Clinical, histological or non-invasive diagnosis of cirrhosis, according to the&#xD;
             American Association for the Study of Liver Diseases, AASLD criteria) [15].&#xD;
&#xD;
          -  Child Pugh A or B (ANNEX II). Child Pugh classification should be calculated based on&#xD;
             clinical findings and laboratory results during the selection period.&#xD;
&#xD;
          -  Chronic Hepatitis C, defined as positive viremia with real time PCR method.&#xD;
&#xD;
          -  Current or prior treatment with DAA, including any interferon-free scheme, either in a&#xD;
             clinical protocol or treated in the daily practice.&#xD;
&#xD;
          -  Co-infection with HIV infection is allowed or Hepatitis B.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  • Prior diagnosis of Hepatocellular to treatment with DAA.&#xD;
&#xD;
               -  Previous liver transplantation.&#xD;
&#xD;
               -  Drug addiction, medical, psychological or social problems that may interfere with&#xD;
                  the patient's participation in the study or evaluation of the results.&#xD;
&#xD;
               -  Pregnancy and/or breastfeeding.&#xD;
&#xD;
               -  Close relationship with the research center; eg close family member of the&#xD;
                  researcher, dependent (eg employee or student research center that could access&#xD;
                  study records and data CRF).&#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_contact>
    <last_name>Maria Julia Cremona</last_name>
    <email>MCREMONA@austral.edu.ar</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Marcelo Silva, MD</last_name>
    <email>msilva@cas.austral.edu.ar</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Universidad Austral</name>
      <address>
        <city>Pilar</city>
        <state>Buenos Aires</state>
        <zip>1629</zip>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marcelo Silva, MD</last_name>
      <email>msilva@cas.austral.edu.ar</email>
    </contact>
    <contact_backup>
      <last_name>Federico Piñero, MD, MSCE</last_name>
      <email>fpinerof@cas.austral.edu.ar</email>
    </contact_backup>
    <investigator>
      <last_name>Marcelo Silva, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Argentina</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 12, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 14, 2018</study_first_posted>
  <last_update_submitted>December 14, 2018</last_update_submitted>
  <last_update_submitted_qc>December 14, 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>Austral University, Argentina</investigator_affiliation>
    <investigator_full_name>Maria Julia Cremona</investigator_full_name>
    <investigator_title>UIC staff</investigator_title>
  </responsible_party>
  <keyword>direct acting antivirals</keyword>
  <keyword>hepatitis c</keyword>
  <keyword>hepatocellular carcinoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Drug-Related Side Effects and Adverse Reactions</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antiviral Agents</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03775798
org study id: 17-062
nct id: NCT03775798
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The main risk factor for development of hepatocellular carcinoma (HCC) is cirrhosis of any
      etiology, with an annual incidence risk between 1-6%; currently the leading cause of death in
      patients with cirrhosis and the 2nd cause of death by cancer worldwide. Chronic hepatitis C
      (HCV) is the first single cause associated to cirrhosis and HCC in the Western world.

      With the advent of new direct antiviral agents (DAA) of chronic HCV infection, virological
      cure generally exceeds 90% of the cases. Previous studies have shown that the incidence of
      HCC is lower in patients with virologic cure after treatment with pegINF schemes. However,
      recently published data, open up more controversy regarding the incidence of HCC after
      virologic cure with DAA. An increasing incidence of HCC after virologic cure in patients
      treated with DAA has been observed, opening a paradox yet unexplained.

      This project proposes to answer the following clinical research question: in patients with
      HCV cirrhosis treated with DAA, is there a change in the incidence of hepatocellular
      carcinoma? To answer this question a prospective longitudinal cohort study of patients with
      Child Pugh A-B cirrhosis will be held at 3 years minimum follow-up.

      A minimum of 210 patients will be included with clinical or histological or non-invasive
      diagnosis of cirrhosis Child Pugh A or B, with HCV treated with DAA and without
      hepatocellular carcinoma at the time of enrollment. From this cohort, patients who develop
      HCC during follow-up will be identified. Routine screening will be done through ultrasound
      every 6 months in all subjects enrolled and the diagnosis of HCC will be according to
      recommendations of European and American guidelines.
Name of the study:

      INCIDENCE OF HEPATOCELLULAR CARCINOMA IN CIRRHOTIC PATIENTS WITH HEPATITIS C INFECTION,
      TRETAED WITH DIRECT ANTIVIRAL AGENTS IN LATIN AMERICA: A MULTICENTER PROSPECTIVE COHORT STUDY

      With the advent of new direct antiviral agents (DAA) of chronic HCV infection, virological
      cure generally exceeds 90% of the cases. Previous studies have shown that the incidence of
      HCC is lower in patients with virologic cure after treatment with pegINF schemes. However,
      recently published data, open up more controversy regarding the incidence of HCC after
      virologic cure with DAA. An increasing incidence of HCC after virologic cure in patients
      treated with DAA has been observed, opening a paradox yet unexplained.

      This project proposes to answer the following clinical research question: in patients with
      HCV cirrhosis treated with DAA, is there a change in the incidence of hepatocellular
      carcinoma? To answer this question a prospective longitudinal cohort study of patients with
      Child Pugh A-B cirrhosis will be held at 3 years minimum follow-up.

      A minimum of 210 patients will be included with clinical or histological or non-invasive
      diagnosis of cirrhosis Child Pugh A or B, with HCV treated with DAA and without
      hepatocellular carcinoma at the time of enrollement. From this cohort, patients who develop
      HCC during follow-up will be identified. Routine screening will be done through ultrasound
      every 6 months in all subjects enrolled and the diagnosis of HCC will be according to
      recommendations of European and American guidelines.

      However, preliminary results presented at the last European Congress of Hepatology in
      Barcelona, Spain, and early published in Journal of Heaptology, open up more controversy
      regarding the incidence of HCC after virologic cure post DAA. An unexpected higher incidence
      and recurrence of HCC after treatment with these new drugs has been observed, opening a
      paradox yet unexplained. Of particular interest then, is to clarify and find if there is a
      change in the incidence of HCC in HCV cirrhosis after treatment with DAA in our region. It is
      relevant on the other hand; that this study would be the first longitudinal cohort study
      evaluating the development of HCC in patients with cirrhosis in Latin America. It is then
      expected that the results would be extremely important to the medical science from this
      region.

      Clinical Research Question In patients with HCV cirrhosis treated DAA, is there a change in
      the incidence of hepatocellular carcinoma? Primary Objective To evaluate the incidence of HCC
      after treatment with DAA in patients with Child Pugh A or B cirrhosis and chronic HCV
      infection.

      Secondary Objectives

      Secondary objectives will be related to:

        -  Incidence of HCC between cured and uncured of HCV with DAA.

        -  Impact of routine screening on survival in patients with HCC.

        -  Risk factors for development of hepatocellular carcinoma in patients with HCV treated
           with DAA.

        -  Adverse events and incidence of cirrhosis decompensation after DAA.
observational model: Cohort
time perspective: Prospective
measure: Incidence of hepatocellular carcinoma after direct-acting antivirals for HCV
time frame: Three year period
description: Cumulative incidence, Hazard ratios (95% CI)
measure: Effectiveness of direct-acting antivirals for HCV
time frame: Three year period
description: Achievement of RVS
measure: Adverse events after direct-acting antivirals for HCV
time frame: Three year period
description: Safety
intervention type: Drug
intervention name: Direct antiviral agents for hepatitis C
description: Direct-acting antivirals for hepatitis C
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Maria Julia Cremona
email: MCREMONA@austral.edu.ar
last name: Marcelo Silva, MD
email: msilva@cas.austral.edu.ar
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Argentina
responsible party type: Principal Investigator
investigator affiliation: Austral University, Argentina
investigator full name: Maria Julia Cremona
investigator title: UIC staff
mesh term: Hepatitis C
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Hepatitis
mesh term: Drug-Related Side Effects and Adverse Reactions
mesh term: Antiviral Agents
sharing ipd: Undecided