Neutrophil Function During Therapy With Protease Inhibitors in Chronic Hepatitis C

NCT ID: NCT02545335

Last Updated: 2023-01-12

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 174 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-11-01
• Study Completion Date: 2020-12-31

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.

Conditions

Chronic Hepatitis C

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Graz

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vanessa Statdlbauer, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Graz

Locations

Department of Internal Medicine, Medical University of Graz

Graz, , Austria

Countries

Austria

References

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.

Reference Type: RESULT

PMID: 26938078 (View on PubMed)

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.

Reference Type: RESULT

PMID: 33352296 (View on PubMed)

Other Identifiers

HCV-neutrophil

Identifier Type: -

Identifier Source: org_study_id