Determinants of Virological Response After Discontinuation of Nucleoside Analogue Therapy in Hepatitis B Patients (STOP)

October 12, 2016 updated by: Alexander Thompson, St Vincent's Hospital Melbourne

Determinants of Sustained Virological Response After Discontinuation of Long-term Nucleoside Analogue Therapy in Chronic Hepatitis B Patients

Evaluation of the rate of sustained virological response among HBeAg-negativechronic hepatitis B patients who discontinue long-term NA therapy.

During this study participants will cease their prescribed medications, this will occur with immediate effect once enrolled into the study. The duration of cessation will be indefinite, unless clinically indicated for NA therapy re-start. Participants will be monitored as per protocol following cessation, monitoring will be by clinic visit and through blood test to monitor virological response. Clinical visits will be at the intervals of week 2, week, 4, week 8, week 12, week 18, following this they will be every 3 months out to 2 years when the participant will have completed the trial. Once the participant has completed the trial they will not commence again, the aim is for an indefinite cessation of NA therapy.

Study Overview

Status

Unknown

Intervention / Treatment

Detailed Description

During this study participants will cease their prescribed medications, this will occur with immediate effect once enrolled into the study. The duration of cessation will be indefinite, unless clinically indicated for NA therapy re-start. Participants will be monitored as per protocol following cessation, monitoring will be by clinic visit and through blood test to monitor virological response. Clinical visits will be at the intervals of week 2, week, 4, week 8, week 12, week 18, following this they will be every 3 months out to 2 years when the participant will have completed the trial. Once the participant has completed the trial they will not commence again, the aim is for an indefinite cessation of NA therapy.

Study Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or Female, age >18 years
  • Subjects must be able to understand and agree to comply with the prescribed intervention (NA cessation), visits and reliably communicate with study personal about adverse events
  • Able to provide informed consent.
  • Chronic Hepatitis B virus infection
  • HBeAg negative at time if initiation of NA therapy
  • Meet current APASL guidelines for consideration of antiviral cessation:
  • uninterrupted NA treatment for >2 years and
  • undetectable serum HBV DNA on three separate occasions >= 6 months apart (undetectable defined by a value < lower limit of detection using a sensitive commercial PCR assay)
  • Normal serum ALT levels (according to the uppers limit of normal of the local laboratory)
  • Minimal to moderate liver fibrosis defined as:
  • METAVIR liver fibrosis stage F0-F3 inclusive prior to initial NA therapy and/or
  • Transient liver elastogram (TLE) (Fibroscan) < /= 9.6 kPa at screening

Exclusion Criteria:

  • HBeAg positive chronic hepatitis B at the time of NA initiation
  • HBV associated extra hepatic manifestations
  • Documented or suspected hepatocellular carcinoma (HCC)
  • History of decompensated liver disease
  • Compensated cirrhosis defined as:
  • METAVIR liver fibrosis stage 4 on pre-treatment biopsy; OR
  • TLE > 9.6 kPa at screening
  • Co-infection with HIV,HCV or HDV
  • Latrogenic or disease related immunosuppression (e.g. treatment with systemic glucocorticoids, TNFa-antibodies, and other immunosuppressive drugs)
  • Significant alcohol consumption (> 30 g/day for women and > 50 g/day for men)
  • Current known history of cancer within 5 years of screening
  • Pregnant or breast feeding
  • Other known significant liver disease (including but not limited to haemochromatosis, autoimmune hepatitis, alcoholic liver disease)
  • Participation in any other interventional trial
  • Poor Venous access
  • Suspected lack of compliance
  • Any medical or social reason which in the opinion of the investigator would make the subject inappropriate for the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nucleoside analogue therapy cessation
To determine if a sustained virological response can be achieved after discontinuation of long-term nucleoside analogue therapy in chronic hepatitis B patients.
Determinants of sustained virological response after discontinuation of long-term nucleoside analogue therapy in chronic hepatitis B patients.
Other Names:
  • Cessation of Nucleoside Analogue Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary aim of this study is to evaluate the rate of sustained virological response among HBeAg-negative chronic hepatitis B patients who discontinue long-term NA therapy. The outcome is to be assessed by serum assay.
Time Frame: Patients will be closely followed for 2 years prospectively, at the following time points; 2 weeks post cessation, 4 weeks, 8 weeks, 12 weeks, 18 weeks, then from 6 months the visits will be 3 monthly out to two years, to observe for virological changes.
Patients will be closely followed for 2 years prospectively, at the following time points; 2 weeks post cessation, 4 weeks, 8 weeks, 12 weeks, 18 weeks, then from 6 months the visits will be 3 monthly out to two years, to observe for virological changes.

Secondary Outcome Measures

Outcome Measure
Time Frame
To identify novel immunological determinants of SVR, the assessment will be by serum assay.
Time Frame: Patients will be closely followed for 2 years prospectively, at the following time points; 2 weeks post cessation, 4 weeks, 8 weeks, 12 weeks, 18 weeks, then from 6 months the visits will be 3 monthly out to two years.
Patients will be closely followed for 2 years prospectively, at the following time points; 2 weeks post cessation, 4 weeks, 8 weeks, 12 weeks, 18 weeks, then from 6 months the visits will be 3 monthly out to two years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Alexander Thompson, MD, St Vincent's Hospital Melbourne

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2014

Primary Completion (Anticipated)

May 1, 2018

Study Completion (Anticipated)

May 1, 2018

Study Registration Dates

First Submitted

October 15, 2015

First Submitted That Met QC Criteria

October 18, 2015

First Posted (Estimate)

October 20, 2015

Study Record Updates

Last Update Posted (Estimate)

October 14, 2016

Last Update Submitted That Met QC Criteria

October 12, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Chronic Hepatitis B.

Clinical Trials on Nucleoside Analogue therapy

3
Subscribe