<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/NCT02196064</url>
  </required_header>
  <id_info>
    <org_study_id>hEPAtic</org_study_id>
    <nct_id>NCT02196064</nct_id>
  </id_info>
  <brief_title>Hepatic Safety of Eviplera® in HIV/Hepatitis C (HCV)-Coinfected Patients Without HCV Treatment in the &quot;The HEPAVIR HEPATIC SAFETY Cohort.&quot;</brief_title>
  <acronym>hEPAtic</acronym>
  <official_title>Hepatic Safety of Eviplera® in HIV/Hepatitis C (HCV)-Coinfected Patients Without HCV Treatment in the &quot;The HEPAVIR HEPATIC SAFETY Cohort.&quot; hEPAtic Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundación Pública Andaluza Progreso y Salud</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Andalusian Network for Design and Translation of Advanced Therapies</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the incidence of grade 3 or 4 transaminase elevations or grade 4 total bilirubin&#xD;
      elevations (hepatic toxicity) during the first 48 weeks of antiretroviral therapy with the&#xD;
      combination of rilpivirine (25mg), tenofovir (245mg) and emtricitabine (200mg), in a&#xD;
      single-tablet regimen (Eviplera®) in human immunodeficiency virus (HIV)/hepatitis C virus&#xD;
      (HCV)-coinfected subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a retrospective analysis of the prospective multicenter, observational &quot;HEPAVIR&#xD;
      HEPATIC SAFETY Cohort&quot; (NCT01908660), in which the hepatic safety of the three-drug&#xD;
      combination TDF/FTC/RPV will be assessed. A total of 176 patients will be included in this&#xD;
      study, as well as 352 patients naive for RPV who initiated any ART that does not include RPV,&#xD;
      who will serve as control group.&#xD;
&#xD;
      The main objective is to evaluate the incidence of grade 3 or 4 transaminase elevations or&#xD;
      grade 4 total bilirubin elevations (hepatic toxicity) during the first 48 weeks of&#xD;
      antiretroviral therapy with the combination of rilpivirine (25mg), tenofovir (245mg) and&#xD;
      emtricitabine (200mg), in a single-tablet regimen (Eviplera®) in human immunodeficiency virus&#xD;
      (HIV)/hepatitis C virus (HCV)-coinfected subjects.&#xD;
&#xD;
      Variables collected within in the cohort:&#xD;
&#xD;
        -  Demographic variable: age, sex.&#xD;
&#xD;
        -  Variables related to hepatitis C virus-infection: infection route, genotype, grade of&#xD;
           hepatic fibrosis and method used for its determination, baseline Child-Pugh index in&#xD;
           patients with cirrhosis, previous hepatic decompensations.&#xD;
&#xD;
        -  Variables related to HIV-infection: CDC clinical category, HIV viral load, CD4 cell&#xD;
           count, previous and new antiretroviral drugs.&#xD;
&#xD;
        -  Blood test: AST, ALT platelets, cholesterol, bilirubin, gamma-glutamyltransferase,&#xD;
           alkaline phosphatase, creatinine.&#xD;
&#xD;
        -  Other variables: alcohol intake, self-reported adverse events, abnormal clinical&#xD;
           findings.&#xD;
&#xD;
        -  Cause of discontinuing antiviral when applicable.&#xD;
&#xD;
      Endpoints&#xD;
&#xD;
        1. Primary endpoint: Emergence of grade 3-4 TEs/grade 4 TBEs (hepatic toxicity) from&#xD;
           baseline to week 48.&#xD;
&#xD;
        2. Secondary endpoints&#xD;
&#xD;
             -  Emergence of hepatic adverse events.&#xD;
&#xD;
             -  Drug interruptions due to liver toxicity.&#xD;
&#xD;
             -  Development of hepatic decompensations.&#xD;
&#xD;
             -  CD4 and viral load changes from baseline to week 48.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of hepatic events</measure>
    <time_frame>First 48 weeks of antiretroviral therapy</time_frame>
    <description>Number of patients with grade 3 or 4 transaminase elevations or grade 4 total bilirubin elevations (hepatic toxicity) during the first 48 weeks of antiretroviral therapy with the combination of rilpivirine (25mg), tenofovir (245mg) and emtricitabine (200mg), in a single-tablet regimen (Eviplera®) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected subjects.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of hepatic events between exposed and unexposed to Eviplera®</measure>
    <time_frame>First 48 weeks of antiretroviral therapy</time_frame>
    <description>We evaluated the following parameters between subjets exposed and unexposed to Eviplera®&#xD;
Incidence of hepatic toxicity&#xD;
Incidence of hepatic adverse events.&#xD;
Proportion of subjects who interrupt treatment due to liver toxicity according to Eviplera® exposure&#xD;
We will evaluated this parameters taking account the impact of baseline liver fibrosis/cirrhosis on liver toxicity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Viral Kinetics and Immune response</measure>
    <time_frame>48 weeks of antiretroviral therapy</time_frame>
    <description>Viral kinetics.- We compare the viral load between patients exposed and not exposed with Eviplera.&#xD;
Immune response.- We compare number of CD4 cells between patients exposed and not exposed with Eviplera</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">519</enrollment>
  <condition>Human Immunodeficiency Virus (HIV) Hepatitis C Virus (HCV) Coinfected Subjects</condition>
  <arm_group>
    <arm_group_label>Safety of the three-drug combination TDF/FTC/RPV</arm_group_label>
    <description>A total of 176 patients will be included in this study, as well as 352 patients naive for RPV who initiated any ART that does not include RPV, who will serve as control group.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        A total of 176 patients will be included in this study, as well as 352 patients naive for&#xD;
        RPV who initiated any ART that does not include RPV, who will serve as control group.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ≥ 18 years old.&#xD;
&#xD;
          -  Chronic HIV-1 infection, as diagnosed on the basis of the presence of serum HIV&#xD;
             antibodies detected by EIA and western-blot.&#xD;
&#xD;
          -  Chronic HCV infection as proven by detecting HCV antibodies in plasma, as well as&#xD;
             detectable plasma HCV-RNA by PCR.&#xD;
&#xD;
          -  To start a new ART regimen during the study period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with hepatotoxic events in the 2 months previous to Eviplera® treatment.&#xD;
&#xD;
          -  Acute infections or uncontrolled chronic infection in the two months previous to&#xD;
             Eviplera® treatment.&#xD;
&#xD;
          -  Concomitant use of any drug with potential drug-drug interaction with Eviplera®.&#xD;
&#xD;
          -  Documented resistance to study drugs.&#xD;
&#xD;
          -  Concomitant therapy including anti-HCV agents, cytotoxic chemotherapy or&#xD;
             immunosuppressors during Eviplera® treatment.&#xD;
&#xD;
          -  Subjects taking part in any other clinical trial using an investigational product,&#xD;
             with the exception of studies where the treatment studied have stopped for more than&#xD;
             12 weeks before Eviplera® treatment.&#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>Juan Antonio Pineda Vergara</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital Universitario Virgen de Valme</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Antonio Rivero Román</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital Universitario Reina Sofía</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dolores Merino Muñoz</last_name>
    <role>Principal Investigator</role>
    <affiliation>Complejo Hospitalario de Especialidades Juan Ramón Jimenez</affiliation>
  </overall_official>
  <overall_official>
    <last_name>María José Rios Villega</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Universitario Virgen Macarena</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Francisco Téllez Pérez</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital La Línea de la Concepción</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Inés Pérez Camacho</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital de Poniente</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Antonio Collado Romacho</last_name>
    <role>Principal Investigator</role>
    <affiliation>Complejo Hospitario Torrecárdenas</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Josefa Ruiz Morales</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Universitario Virgen de la Victoria</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marcial Delgado Fernández</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Regional de Malaga</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Leopoldo Muñoz Medina</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Universitario San Cecilio</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Francisco Vera Méndez</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Santa María de Rosell</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nuria Espinosa Aguilera</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospitales Universitarios Virgen del Rocío</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Iganacio Santos Gil</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fundación de Investigación Biomédica - Hospital Universitario de La Princesa</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Juan González García</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Universitario La Paz</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Antonio Vergara de Campos</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Universitario de Puerto Real</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Juan Berenguer Berenguer</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Universitario Gregorio Marañón</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Federico Pulido Ortega</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital 12 de Octubre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fundación Pública Andaluza Progreso y Salud</name>
      <address>
        <city>Sevilla</city>
        <zip>41092</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>August 2015</verification_date>
  <study_first_submitted>July 15, 2014</study_first_submitted>
  <study_first_submitted_qc>July 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <last_update_submitted>August 4, 2015</last_update_submitted>
  <last_update_submitted_qc>August 4, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 5, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV HCV antiretroviral</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>Acquired Immunodeficiency Syndrome</mesh_term>
    <mesh_term>HIV Infections</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/NCT02196064
org study id: hEPAtic
nct id: NCT02196064
lead sponsor: 
collaborator: 
has dmc: No
To evaluate the incidence of grade 3 or 4 transaminase elevations or grade 4 total bilirubin
      elevations (hepatic toxicity) during the first 48 weeks of antiretroviral therapy with the
      combination of rilpivirine (25mg), tenofovir (245mg) and emtricitabine (200mg), in a
      single-tablet regimen (Eviplera®) in human immunodeficiency virus (HIV)/hepatitis C virus
      (HCV)-coinfected subjects.
This is a retrospective analysis of the prospective multicenter, observational "HEPAVIR
      HEPATIC SAFETY Cohort" (NCT01908660), in which the hepatic safety of the three-drug
      combination TDF/FTC/RPV will be assessed. A total of 176 patients will be included in this
      study, as well as 352 patients naive for RPV who initiated any ART that does not include RPV,
      who will serve as control group.

      The main objective is to evaluate the incidence of grade 3 or 4 transaminase elevations or
      grade 4 total bilirubin elevations (hepatic toxicity) during the first 48 weeks of
      antiretroviral therapy with the combination of rilpivirine (25mg), tenofovir (245mg) and
      emtricitabine (200mg), in a single-tablet regimen (Eviplera®) in human immunodeficiency virus
      (HIV)/hepatitis C virus (HCV)-coinfected subjects.

      Variables collected within in the cohort:

        -  Demographic variable: age, sex.

        -  Variables related to hepatitis C virus-infection: infection route, genotype, grade of
           hepatic fibrosis and method used for its determination, baseline Child-Pugh index in
           patients with cirrhosis, previous hepatic decompensations.

        -  Variables related to HIV-infection: CDC clinical category, HIV viral load, CD4 cell
           count, previous and new antiretroviral drugs.

        -  Blood test: AST, ALT platelets, cholesterol, bilirubin, gamma-glutamyltransferase,
           alkaline phosphatase, creatinine.

        -  Other variables: alcohol intake, self-reported adverse events, abnormal clinical
           findings.

        -  Cause of discontinuing antiviral when applicable.

      Endpoints

        1. Primary endpoint: Emergence of grade 3-4 TEs/grade 4 TBEs (hepatic toxicity) from
           baseline to week 48.

        2. Secondary endpoints

             -  Emergence of hepatic adverse events.

             -  Drug interruptions due to liver toxicity.

             -  Development of hepatic decompensations.

             -  CD4 and viral load changes from baseline to week 48.
observational model: Cohort
time perspective: Retrospective
measure: Incidence of hepatic events
time frame: First 48 weeks of antiretroviral therapy
description: Number of patients with grade 3 or 4 transaminase elevations or grade 4 total bilirubin elevations (hepatic toxicity) during the first 48 weeks of antiretroviral therapy with the combination of rilpivirine (25mg), tenofovir (245mg) and emtricitabine (200mg), in a single-tablet regimen (Eviplera®) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected subjects.
measure: Comparison of hepatic events between exposed and unexposed to Eviplera®
time frame: First 48 weeks of antiretroviral therapy
description: We evaluated the following parameters between subjets exposed and unexposed to Eviplera®
Incidence of hepatic toxicity
Incidence of hepatic adverse events.
Proportion of subjects who interrupt treatment due to liver toxicity according to Eviplera® exposure
We will evaluated this parameters taking account the impact of baseline liver fibrosis/cirrhosis on liver toxicity.
measure: Viral Kinetics and Immune response
time frame: 48 weeks of antiretroviral therapy
description: Viral kinetics.- We compare the viral load between patients exposed and not exposed with Eviplera.
Immune response.- We compare number of CD4 cells between patients exposed and not exposed with Eviplera
arm group label: Safety of the three-drug combination TDF/FTC/RPV
description: A total of 176 patients will be included in this study, as well as 352 patients naive for RPV who initiated any ART that does not include RPV, who will serve as control group.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Juan Antonio Pineda Vergara
role: Study Chair
affiliation: Hospital Universitario Virgen de Valme
last name: Antonio Rivero Román
role: Study Chair
affiliation: Hospital Universitario Reina Sofía
last name: Dolores Merino Muñoz
role: Principal Investigator
affiliation: Complejo Hospitalario de Especialidades Juan Ramón Jimenez
last name: María José Rios Villega
role: Principal Investigator
affiliation: Hospital Universitario Virgen Macarena
last name: Francisco Téllez Pérez
role: Principal Investigator
affiliation: Hospital La Línea de la Concepción
last name: Inés Pérez Camacho
role: Principal Investigator
affiliation: Hospital de Poniente
last name: Antonio Collado Romacho
role: Principal Investigator
affiliation: Complejo Hospitario Torrecárdenas
last name: Josefa Ruiz Morales
role: Principal Investigator
affiliation: Hospital Universitario Virgen de la Victoria
last name: Marcial Delgado Fernández
role: Principal Investigator
affiliation: Hospital Regional de Malaga
last name: Leopoldo Muñoz Medina
role: Principal Investigator
affiliation: Hospital Universitario San Cecilio
last name: Francisco Vera Méndez
role: Principal Investigator
affiliation: Hospital Santa María de Rosell
last name: Nuria Espinosa Aguilera
role: Principal Investigator
affiliation: Hospitales Universitarios Virgen del Rocío
last name: Iganacio Santos Gil
role: Principal Investigator
affiliation: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
last name: Juan González García
role: Principal Investigator
affiliation: Hospital Universitario La Paz
last name: Antonio Vergara de Campos
role: Principal Investigator
affiliation: Hospital Universitario de Puerto Real
last name: Juan Berenguer Berenguer
role: Principal Investigator
affiliation: Hospital Universitario Gregorio Marañón
last name: Federico Pulido Ortega
role: Principal Investigator
affiliation: Hospital 12 de Octubre
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
mesh term: Hepatitis