Clinical trial NCT02969668: Interferon-free Antiviral Treatment of Chronic Hepatitis C Virus Infection Among Opioid-substituted Patients
Official title: Effectiveness and Safety of Interferon-free Antiviral Regimens for the Treatment of Chronic Hepatitis C Virus Infection Among Opioid-substituted Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatitis C, Chronic
Opioid-Related Disorders
Keywords: opioid substitution treatment
interferon-free direct acting antivirals
hepatitis c therapy
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2016-11-21
Enrollment: 326
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with chronic HCV-genotype 1-6, aged over 18 years, who are for a minimum of 3 months in opioid substitution treatment and who are beginning an antiviral HCV treatment with interferon-free direct acting antivirals (IFN-free DAAs)

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* aged over 18 years
* opioid dependence according to ICD-10
* admission to opioid substitution treatment for at least 3 months
* Chronic hepatitis C infection with genotype 1-6
* eligibility for antiviral HCV treatment with IFN-free DAAs according to the respective summary of product characteristics (SmPC)

Exclusion Criteria:

* missing eligibility for antiviral HCV treatment with IFN-free DAAs according to SmPC
* inability of the patient to participate in the study (e.g. due to severe mental impairment)
* missing patient-signed written informed consent

Primary outcomes:
measure: Sustained virological response
timeFrame: through study completion, up to 36 weeks after baseline
Secondary outcomes:
measure: Adverse events
timeFrame: through study completion, up to 36 weeks after baseline
measure: Patient-reported physical health status, as measured with the Opiate Treatment Index Health Scale (OTI-HSS)
timeFrame: through study completion, up to 36 weeks after baseline
measure: Patient-reported mental health status, as measured with the brief symptom inventory 18 (BSI-18)
timeFrame: through study completion, up to 36 weeks after baseline
measure: Health related quality of life, as measured with the short form 12 (SF-12, version 1)
timeFrame: through study completion, up to 36 weeks after baseline
measure: Questionnaire on patient-reported fatigue and subjective cognitive impairments
timeFrame: through study completion, up to 36 weeks after baseline
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Praxiszentrum im Tal (PIT)
state: Bavaria
city: Berlin
country: Germany
facility: Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH
city: Berlin
country: Germany
facility: Praxisgemeinschaft Turmstraße
city: Berlin
country: Germany
facility: Praxis Gabriele U. Bellmann/ Norbert E. Lyonn Fachärzte für Allgemeinmedizin
city: Berlin
country: Germany
facility: Praxis Micus
city: Berlin
country: Germany
facility: Praxiszentrum Kaiserdamm
city: Berlin
country: Germany
facility: Praxis D. Höpner/M. H. Besson
city: Bremen
country: Germany
facility: Gemeinschaftspraxis Dres. Tietje, Koc, Schulte
city: Frankfurt
country: Germany
facility: MainFachArzt
city: Hamburg
country: Germany
facility: Medizentrum Hamburg
city: Hanover
country: Germany
facility: Kompetenzzentrum für Suchtmedizin und Infektiologie
city: Kassel
country: Germany
facility: Praxiszentrum Friedrichsplatz
city: Köln
country: Germany
facility: Gemeinschaftspraxis Gotenring
city: Muenchen
country: Germany
facility: Praxis Lebentrau
city: Munich
country: Germany
facility: CIM GmbH Infektiologische Praxisgemeinschaft Busch/Christensen
city: Munich
country: Germany
facility: Schwerpunktpraxis "Concept"
city: Stuttgart
country: Germany
facility: Dres. Ulmer, Frietsch, Müller, Roll
city: Wuppertal
country: Germany
facility: PG Mauruschat/Weilbrenner
Study officials:
affiliation: Universitätsklinikum Hamburg-Eppendorf
name: Jens Reimer, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: