Surveillance for Antiviral Resistant Variants in Chronic Hepatitis C Patients (SEARCH-C)

This is a multi-centre prospective longitudinal cohort study with the aim of collecting and storing clinical data, patient blood, DNA and PBMCs to examine outcomes related to drug resistance, drug monitoring and host genetics in the era of directly acting antiviral drugs for hepatitis C therapy.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C Infection

Detailed Description

1. To analyse for resistance-associated HCV variants in DAA-naïve HCV patients using population and ultra-deep pyrosequencing (UDPS). Resistance associated variants will be analysed by qualitative and quantitative methods both pre-treatment and on-treatment.
2. To determine whether in the absence of drug pressure there is variation in the prevalence of naturally occurring resistance associated variants.
3. To correlate the presence and frequency of baseline resistance-associated variants with the response to therapy with DAA-based triple therapy regimens for HCV.
4. To identify predictors of emergent DAA resistance and treatment failure during therapy with DAA-based combination strategies, including virological, clinical and immunological factors.
5. To characterize the natural history of HCV resistance associated variants that are selected during antiviral therapy after the withdrawal of treatment.
6. To establish a cohort of DAA-treatment failure patients suitable for re-treatment studies.
7. To establish a tissue repository of serum and PBMCs from well-characterized patients treated with DAA-based triple therapy to allow future examination of the role of other variables that may potentially impact on the outcomes of DAA based therapy and development of RAVs.

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

• Study Contact: Name: Amanda Erratt; Phone Number: +61 2 9385 0882; Email: aerratt@kirby.unsw.edu.au
• Study Contact Backup: Name: Pip Marks, BSc MPH (Hons); Phone Number: +61 2 9385 0886; Email: pmarks@kirby.unsw.edu.au

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • St Vincent's Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3065
      • St Vincent's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

An anticipated 100 participants will be recruited from 2 study sites: St Vincent's Hospital, Sydney; St Vincent's Hospital, Melbourne.

Description

Inclusion Criteria:

• Chronic hepatitis C infection
• Commencing or expected to commence DAA-based HCV treatment within the next year
• IFN treatment-naïve or IFN treatment-experienced
• Provision of written, informed consent

Exclusion Criteria:

• In the opinion of the investigator that the patient is not able to provide informed consent
• Inability or unwillingness to comply with study collection requirements

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of HCV resistance associated variants (RAVs) and the incidence of RAVs arising during therapy.	Descriptive statistics will be used to describe RAVs using standard international nomenclature and presented in table form. Baseline clinical and demographic data on subjects will be presented, as will rates of treatment failure and reasons for failure.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Factors associated with treatment failure due to virological breakthrough / relapse.	Multivariable logistic regression modelling with backwards elimination will be used to identify factors associated with this.	Baseline

Collaborators and Investigators

• Sponsor: Kirby Institute
• Collaborators: Merck Sharp & Dohme LLC; The University of New South Wales
• Investigators: Principal Investigator: Gail Dr Matthews, MBChB, MRCP (UK), FRACP, PhD, The University of New South Wales

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2012
• Primary Completion (Actual): June 1, 2022
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: February 16, 2014
• First Submitted That Met QC Criteria: February 18, 2014
• First Posted (Estimated): February 19, 2014

Study Record Updates

• Last Update Posted (Actual): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Hepatitis C, chronic
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Chronic Disease; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic
• Other Study ID Numbers: VHCRP1107