Clinical trial NCT02545335: Neutrophil Function During Therapy With Protease Inhibitors in Chronic Hepatitis C
Official title: Neutrophil Function During Combination Therapy With Protease Inhibitors in Chronic Hepatitis C
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Hepatitis C
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2015-09-09
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: patients with chronic hepatitis C undergoing antiviral therapy

Brief summary: The aim of this study is to characterize neutrophil function in patients undergoing chronic hepatitis C triple therapy with protease inhibitors in comparison to dual therapy with peginterferon and ribavirin and with interferon free treatment regimen to thereby elucidate the possible mechanisms of protease-inhibitor associated infections.

Detailed description: Chronic hepatitis C infection (CHC) is a major health problem, potentially leading to liver related mortality via complications of liver cirrhosis or hepatocellular carcinoma, and affects more than 185 million persons worldwide. Antiviral therapy evolved during the past 25 years from standard interferon, the combination with ribavirin and pegylated interferon (P/R) to the addition of protease inhibitors and is currently on the edge to an interferon-free era with the first such substances being approved in 2014. However, current standard therapy for CHC genotype 1 patients without cirrhosis consists of ribavirin and pegylated interferon (P/R) in combination with boceprevir (BOC) or telaprevir (TPV), which are direct acting antivirals and represent the first-generation protease inhibitors.

Triple therapy for CHC has been reported to be associated with a quantitative and qualitative increase in treatment-related (serious) adverse events compared to the former standard therapy without protease-inhibitors. Moreover, reports of serious infectious complications during triple therapy - especially in patients with acquired immune deficiencies like liver cirrhosis - that lead to considerable morbidity and mortality, have accumulated recently. The mechanisms of this increased susceptibility to infections remain unclear. However, BOC is known to inhibit neutrophil elastase activity.

Aims of this study were therefore to analyse infections that occurred in CHC outpatients during therapy in the study centre, to prospectively characterize neutrophil function in patients undergoing CHC triple therapy in comparison to dual therapy with peginterferon and ribavirin and to thereby elucidate the possible mechanisms of protease-inhibitor associated infections.

Eligibility criteria: Inclusion Criteria:

* chronic hepatitis C
* planned antiviral therapy

Exclusion Criteria:

* immunosuppressive medication
* active infection at baseline
* treatment with antibiotics within the last two weeks

Primary outcomes:
measure: neutrophil phagocytosis
timeFrame: 12 weeks
Secondary outcomes:
measure: number of infections
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Department of Internal Medicine, Medical University of Graz
Study officials:
affiliation: Medical University of Graz
name: Vanessa Statdlbauer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Spindelboeck W, Horvath A, Tawdrous M, Schmerbock B, Zettel G, Posch A, Streit A, Jurse P, Lemesch S, Horn M, Wuensch G, Stiegler P, Stauber RE, Leber B, Stadlbauer V. Triple Therapy with First Generation Protease Inhibitors for Hepatitis C Markedly Impairs Function of Neutrophil Granulocytes. PLoS One. 2016 Mar 3;11(3):e0150299. doi: 10.1371/journal.pone.0150299. eCollection 2016.
citation: Leber B, Balazs I, Horvath A, Posch A, Streit A, Spindelbock W, Feldbacher N, Stiegler P, Stauber RE, Rechberger GN, Kollroser M, Sattler W, Nusshold C, Stadlbauer V. Direct acting antiviral therapy rescues neutrophil dysfunction and reduces hemolysis in hepatitis C infection. Transl Res. 2021 Jun;232:103-114. doi: 10.1016/j.trsl.2020.12.005. Epub 2020 Dec 19.