<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/NCT02969668</url>
  </required_header>
  <id_info>
    <org_study_id>AI444-366</org_study_id>
    <nct_id>NCT02969668</nct_id>
  </id_info>
  <brief_title>Interferon-free Antiviral Treatment of Chronic Hepatitis C Virus Infection Among Opioid-substituted Patients</brief_title>
  <acronym>INFO</acronym>
  <official_title>Effectiveness and Safety of Interferon-free Antiviral Regimens for the Treatment of Chronic Hepatitis C Virus Infection Among Opioid-substituted Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitätsklinikum Hamburg-Eppendorf</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Universitätsklinikum Hamburg-Eppendorf</source>
  <brief_summary>
    <textblock>
      The primary objective of study will be to evaluate the effectiveness of interferon-free&#xD;
      direct acting antivirals (IFN-free DAAs) in the treatment of chronic hepatitis C virus (HCV)&#xD;
      among patients in opioid-substitution treatment (OST). We hypothesize that rates of sustained&#xD;
      virological response will be comparable to non-OST populations. Secondary objectives include&#xD;
      the evaluation of safety data, patients' adherence and patient reported outcome measures like&#xD;
      functioning (disability), satisfaction with the treatment, health status, general health&#xD;
      perceptions and health-related quality of life.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The new interferon-free antiviral regimens for the treatment of chronic hepatitis C (CHC)&#xD;
      infections achieve impressive sustained virological response (SVR) rates beyond 90%, with&#xD;
      shorter treatment duration and reduced side effects, irrespective of previous treatment&#xD;
      history or presence of advanced liver diseases.&#xD;
&#xD;
      In Europe, the majority of HCV infections have been acquired and transmitted through&#xD;
      injecting drug use - therefore, people who inject drugs (PWID) represent the majority of&#xD;
      individuals with CHC infections in the Western industrialized cultures. There are excellent&#xD;
      therapeutic options for those PWID who are in OST, as the frequent treatment provider-patient&#xD;
      contact allows regular diagnoses, a continuing monitoring, and a sustainable management of&#xD;
      HCV-infection among these patients. However, despite the growing evidence that patients in&#xD;
      OST can successfully be treated for HCV, the treatment uptake among this predominant risk&#xD;
      group is still very low. The current evidence from non-drug using populations only have a&#xD;
      limited impact on the willingness of physicians providing opioid substitution treatment&#xD;
      (OST), hepatologists and infectiologists to provide antiviral HCV treatment with IFN-free&#xD;
      DAAs and on the willingness of OST patients to enter such treatment. Accordingly, data on the&#xD;
      effectiveness and safety of antiviral HCV treatment regimens with IFN-free DAAs among this&#xD;
      relevant patient group are urgently needed. The aim of this prospective cohort study is to&#xD;
      assess the effectiveness, safety and patient reported outcome measures of IFN-free DAAs for&#xD;
      the treatment of CHC among OST patients.&#xD;
&#xD;
      The primary objective of this open-label, observational, prospective cohort study will be to&#xD;
      evaluate the effectiveness of IFN-free DAAs regimens for the treatment of chronic&#xD;
      HCV-infection among OST patients in real life clinical settings.&#xD;
&#xD;
      Patients will be treated for chronic HCV with any kind of registered IFN-free DAA protocol&#xD;
      and in accordance with the respective SmPC. This ensures that that dosing and schedule are&#xD;
      supported by Phase I or later research. The study physician will make any medical decisions&#xD;
      with regard to type of medication and doses. The individual treatment duration depends on the&#xD;
      respective treatment protocol. The study physician is responsible for any medical decision&#xD;
      and will document treatment dosage, treatment schedule, treatment duration and outcome.&#xD;
&#xD;
      Effectiveness is defined as sustained virological response at week 12 and week 24 after end&#xD;
      of treatment (SVR12 and SVR24). SVR rates will be compared with the literature on&#xD;
      non-substance using populations on the basis of two-sided 95% confidence intervals. The&#xD;
      sample size calculation revealed, that 295 OST patients (HCV treatment&#xD;
      naïve/Non-responder/Relapser) eligible for treatment with IFN-free DAAs (according to the&#xD;
      summary of product (SmPC)) have to be included. To account for dropouts, we consider an&#xD;
      over-recruitment of 10%, resulting in 325 patients to be recruited.&#xD;
&#xD;
      Secondary objectives include the collection of safety data during the treatment phase until&#xD;
      SVR12, patients' adherence, and patient reported outcome measures like functioning&#xD;
      (disability), satisfaction with the treatment, health status, general health perceptions and&#xD;
      health-related quality of life.&#xD;
&#xD;
      All analyses - effectiveness and safety - will be conducted as intention-to-treat (ITT) as&#xD;
      well as per protocol (PP) analyses. The ITT sample is defined as the number of patients&#xD;
      starting treatment (first dose), whereas the PP sample includes only patients with complete&#xD;
      data for SVR24.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2016</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">October 2018</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>24 Weeks</target_duration>
  <primary_outcome>
    <measure>Sustained virological response</measure>
    <time_frame>through study completion, up to 36 weeks after baseline</time_frame>
    <description>Sustained virological response (SVR), defined as undetectable HCV RNA, will be assessed up to 36 weeks after baseline The individual treatment duration depends on the respective treatment protocol and varies between 8 and 24 weeks.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>through study completion, up to 36 weeks after baseline</time_frame>
    <description>An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation subject administered study drug and that does not necessarily have a causal relationship with this treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient-reported physical health status, as measured with the Opiate Treatment Index Health Scale (OTI-HSS)</measure>
    <time_frame>through study completion, up to 36 weeks after baseline</time_frame>
    <description>Patient-reported physical health status, as measured with the Opiate Treatment Index Health Scale (OTI-HSS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient-reported mental health status, as measured with the brief symptom inventory 18 (BSI-18)</measure>
    <time_frame>through study completion, up to 36 weeks after baseline</time_frame>
    <description>Patient-reported mental health status, as measured with the brief symptom inventory 18 (BSI-18)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health related quality of life, as measured with the short form 12 (SF-12, version 1)</measure>
    <time_frame>through study completion, up to 36 weeks after baseline</time_frame>
    <description>Health related quality of life, as measured with the short form 12 (SF-12, version 1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Questionnaire on patient-reported fatigue and subjective cognitive impairments</measure>
    <time_frame>through study completion, up to 36 weeks after baseline</time_frame>
    <description>This is a self-developed questionnaire with 12 items (5 items on fatigue, and 7 items on subjective cognitive deficits), each item to be rated on a 5-point Likert-Scale.</description>
  </secondary_outcome>
  <enrollment type="Actual">326</enrollment>
  <condition>Hepatitis C, Chronic</condition>
  <condition>Opioid-Related Disorders</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with chronic HCV-genotype 1-6, aged over 18 years, who are for a minimum of 3&#xD;
        months in opioid substitution treatment and who are beginning an antiviral HCV treatment&#xD;
        with interferon-free direct acting antivirals (IFN-free DAAs)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  aged over 18 years&#xD;
&#xD;
          -  opioid dependence according to ICD-10&#xD;
&#xD;
          -  admission to opioid substitution treatment for at least 3 months&#xD;
&#xD;
          -  Chronic hepatitis C infection with genotype 1-6&#xD;
&#xD;
          -  eligibility for antiviral HCV treatment with IFN-free DAAs according to the respective&#xD;
             summary of product characteristics (SmPC)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  missing eligibility for antiviral HCV treatment with IFN-free DAAs according to SmPC&#xD;
&#xD;
          -  inability of the patient to participate in the study (e.g. due to severe mental&#xD;
             impairment)&#xD;
&#xD;
          -  missing patient-signed written informed consent&#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>Jens Reimer, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universitätsklinikum Hamburg-Eppendorf</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Praxiszentrum im Tal (PIT)</name>
      <address>
        <city>Munich</city>
        <state>Bavaria</state>
        <zip>80331</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH</name>
      <address>
        <city>Berlin</city>
        <zip>10439</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxisgemeinschaft Turmstraße</name>
      <address>
        <city>Berlin</city>
        <zip>10551</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxis Gabriele U. Bellmann/ Norbert E. Lyonn Fachärzte für Allgemeinmedizin</name>
      <address>
        <city>Berlin</city>
        <zip>10969</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxis Micus</name>
      <address>
        <city>Berlin</city>
        <zip>12043</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxiszentrum Kaiserdamm</name>
      <address>
        <city>Berlin</city>
        <zip>14057</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxis D. Höpner/M. H. Besson</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gemeinschaftspraxis Dres. Tietje, Koc, Schulte</name>
      <address>
        <city>Bremen</city>
        <zip>28719</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MainFachArzt</name>
      <address>
        <city>Frankfurt</city>
        <zip>60329</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizentrum Hamburg</name>
      <address>
        <city>Hamburg</city>
        <zip>22149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kompetenzzentrum für Suchtmedizin und Infektiologie</name>
      <address>
        <city>Hanover</city>
        <zip>30449</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxiszentrum Friedrichsplatz</name>
      <address>
        <city>Kassel</city>
        <zip>34117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gemeinschaftspraxis Gotenring</name>
      <address>
        <city>Köln</city>
        <zip>50679</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxis Lebentrau</name>
      <address>
        <city>Muenchen</city>
        <zip>80331</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CIM GmbH Infektiologische Praxisgemeinschaft Busch/Christensen</name>
      <address>
        <city>Munich</city>
        <zip>48143</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Schwerpunktpraxis &quot;Concept&quot;</name>
      <address>
        <city>Munich</city>
        <zip>80801</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dres. Ulmer, Frietsch, Müller, Roll</name>
      <address>
        <city>Stuttgart</city>
        <zip>70197</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PG Mauruschat/Weilbrenner</name>
      <address>
        <city>Wuppertal</city>
        <zip>42277</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>June 5, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2016</study_first_posted>
  <last_update_submitted>April 27, 2021</last_update_submitted>
  <last_update_submitted_qc>April 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universitätsklinikum Hamburg-Eppendorf</investigator_affiliation>
    <investigator_full_name>Prof. Dr. med. Jens Reimer</investigator_full_name>
    <investigator_title>Prof. Dr. med. Jens Reimer, MBA; Head of Centre for Interdisciplinary Addiction Research (CIAR), Hamburg University</investigator_title>
  </responsible_party>
  <keyword>opioid substitution treatment</keyword>
  <keyword>interferon-free direct acting antivirals</keyword>
  <keyword>hepatitis c therapy</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>Hepatitis C, Chronic</mesh_term>
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Opioid-Related Disorders</mesh_term>
  </condition_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/NCT02969668
org study id: AI444-366
nct id: NCT02969668
lead sponsor: 
collaborator: 
The primary objective of study will be to evaluate the effectiveness of interferon-free
      direct acting antivirals (IFN-free DAAs) in the treatment of chronic hepatitis C virus (HCV)
      among patients in opioid-substitution treatment (OST). We hypothesize that rates of sustained
      virological response will be comparable to non-OST populations. Secondary objectives include
      the evaluation of safety data, patients' adherence and patient reported outcome measures like
      functioning (disability), satisfaction with the treatment, health status, general health
      perceptions and health-related quality of life.
The new interferon-free antiviral regimens for the treatment of chronic hepatitis C (CHC)
      infections achieve impressive sustained virological response (SVR) rates beyond 90%, with
      shorter treatment duration and reduced side effects, irrespective of previous treatment
      history or presence of advanced liver diseases.

      In Europe, the majority of HCV infections have been acquired and transmitted through
      injecting drug use - therefore, people who inject drugs (PWID) represent the majority of
      individuals with CHC infections in the Western industrialized cultures. There are excellent
      therapeutic options for those PWID who are in OST, as the frequent treatment provider-patient
      contact allows regular diagnoses, a continuing monitoring, and a sustainable management of
      HCV-infection among these patients. However, despite the growing evidence that patients in
      OST can successfully be treated for HCV, the treatment uptake among this predominant risk
      group is still very low. The current evidence from non-drug using populations only have a
      limited impact on the willingness of physicians providing opioid substitution treatment
      (OST), hepatologists and infectiologists to provide antiviral HCV treatment with IFN-free
      DAAs and on the willingness of OST patients to enter such treatment. Accordingly, data on the
      effectiveness and safety of antiviral HCV treatment regimens with IFN-free DAAs among this
      relevant patient group are urgently needed. The aim of this prospective cohort study is to
      assess the effectiveness, safety and patient reported outcome measures of IFN-free DAAs for
      the treatment of CHC among OST patients.

      The primary objective of this open-label, observational, prospective cohort study will be to
      evaluate the effectiveness of IFN-free DAAs regimens for the treatment of chronic
      HCV-infection among OST patients in real life clinical settings.

      Patients will be treated for chronic HCV with any kind of registered IFN-free DAA protocol
      and in accordance with the respective SmPC. This ensures that that dosing and schedule are
      supported by Phase I or later research. The study physician will make any medical decisions
      with regard to type of medication and doses. The individual treatment duration depends on the
      respective treatment protocol. The study physician is responsible for any medical decision
      and will document treatment dosage, treatment schedule, treatment duration and outcome.

      Effectiveness is defined as sustained virological response at week 12 and week 24 after end
      of treatment (SVR12 and SVR24). SVR rates will be compared with the literature on
      non-substance using populations on the basis of two-sided 95% confidence intervals. The
      sample size calculation revealed, that 295 OST patients (HCV treatment
      naïve/Non-responder/Relapser) eligible for treatment with IFN-free DAAs (according to the
      summary of product (SmPC)) have to be included. To account for dropouts, we consider an
      over-recruitment of 10%, resulting in 325 patients to be recruited.

      Secondary objectives include the collection of safety data during the treatment phase until
      SVR12, patients' adherence, and patient reported outcome measures like functioning
      (disability), satisfaction with the treatment, health status, general health perceptions and
      health-related quality of life.

      All analyses - effectiveness and safety - will be conducted as intention-to-treat (ITT) as
      well as per protocol (PP) analyses. The ITT sample is defined as the number of patients
      starting treatment (first dose), whereas the PP sample includes only patients with complete
      data for SVR24.
observational model: Cohort
time perspective: Prospective
measure: Sustained virological response
time frame: through study completion, up to 36 weeks after baseline
description: Sustained virological response (SVR), defined as undetectable HCV RNA, will be assessed up to 36 weeks after baseline The individual treatment duration depends on the respective treatment protocol and varies between 8 and 24 weeks.
measure: Adverse events
time frame: through study completion, up to 36 weeks after baseline
description: An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation subject administered study drug and that does not necessarily have a causal relationship with this treatment.
measure: Patient-reported physical health status, as measured with the Opiate Treatment Index Health Scale (OTI-HSS)
time frame: through study completion, up to 36 weeks after baseline
description: Patient-reported physical health status, as measured with the Opiate Treatment Index Health Scale (OTI-HSS)
measure: Patient-reported mental health status, as measured with the brief symptom inventory 18 (BSI-18)
time frame: through study completion, up to 36 weeks after baseline
description: Patient-reported mental health status, as measured with the brief symptom inventory 18 (BSI-18)
measure: Health related quality of life, as measured with the short form 12 (SF-12, version 1)
time frame: through study completion, up to 36 weeks after baseline
description: Health related quality of life, as measured with the short form 12 (SF-12, version 1)
measure: Questionnaire on patient-reported fatigue and subjective cognitive impairments
time frame: through study completion, up to 36 weeks after baseline
description: This is a self-developed questionnaire with 12 items (5 items on fatigue, and 7 items on subjective cognitive deficits), each item to be rated on a 5-point Likert-Scale.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jens Reimer, Prof. Dr.
role: Principal Investigator
affiliation: Universitätsklinikum Hamburg-Eppendorf
facility: 
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country: Germany
responsible party type: Principal Investigator
investigator affiliation: Universitätsklinikum Hamburg-Eppendorf
investigator full name: Prof. Dr. med. Jens Reimer
investigator title: Prof. Dr. med. Jens Reimer, MBA; Head of Centre for Interdisciplinary Addiction Research (CIAR), Hamburg University
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis C, Chronic
mesh term: Virus Diseases
mesh term: Hepatitis
mesh term: Opioid-Related Disorders
sharing ipd: Undecided