Neutrophil Function During Therapy With Protease Inhibitors in Chronic Hepatitis C

Chronic Hepatitis C Clinical Trial

Official title:

Neutrophil Function During Combination Therapy With Protease Inhibitors in Chronic Hepatitis C

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02545335
• Other study ID #: HCV-neutrophil
• Status: Completed
• Start date: November 1, 2014
• Est. completion date: December 31, 2020

Study information

• Verified date: January 2023
• Source: Medical University of Graz
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 174
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• chronic hepatitis C

• planned antiviral therapy

Exclusion Criteria:

• immunosuppressive medication

• active infection at baseline

• treatment with antibiotics within the last two weeks

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Locations

Country	Name	City	State
Austria	Department of Internal Medicine, Medical University of Graz	Graz

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Graz

Country where clinical trial is conducted

Austria, 

References & Publications (2)

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 — View 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 Impai — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	neutrophil phagocytosis	phagocytosis of labelled E.coli	12 weeks
Secondary	number of infections	reported infections	12 weeks