Neutrophil Function During Therapy With Protease Inhibitors in Chronic Hepatitis C

Completed

• Conditions: Chronic Hepatitis C

• Registration Number: NCT02545335
• Lead Sponsor: Medical University of Graz

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.

Study Timeline

• Study Start: 2014-11-01
• Study First Submitted: 2015-07-29
• Study First Submitted QC: 2015-09-07
• Study First Posted: 2015-09-09
• Primary Completion: 2020-12-31
• Study Completion: 2020-12-31
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-11
• Last Update Posted: 2023-01-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 174

Inclusion Criteria

• chronic hepatitis C
• planned antiviral therapy

Exclusion Criteria

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
neutrophil phagocytosis	12 weeks	phagocytosis of labelled E.coli

Secondary Outcome Measures

Name	Time	Method
number of infections	12 weeks	reported infections

Trial Locations

Locations (1)

Department of Internal Medicine, Medical University of Graz; 🇦🇹 Graz, Austria