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

NCT ID: NCT02581033

Last Updated: 2016-10-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2018-05-31

Brief Summary

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.

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.

Conditions

Chronic Hepatitis B.

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Nucleoside Analogue therapy

Intervention Type: DRUG

Determinants of sustained virological response after discontinuation of long-term nucleoside analogue therapy in chronic hepatitis B patients.

Interventions

Nucleoside Analogue therapy

Determinants of sustained virological response after discontinuation of long-term nucleoside analogue therapy in chronic hepatitis B patients.

Intervention Type: DRUG

Other Intervention Names

Cessation of Nucleoside Analogue Therapy

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Health and Medical Research Council, Australia

OTHER

Sponsor Role: collaborator

St Vincent's Hospital Melbourne

OTHER

Sponsor Role: lead

Responsible Party

Alexander Thompson

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alexander Thompson, MD

Role: PRINCIPAL_INVESTIGATOR

St Vincent's Hospital Melbourne

Locations

St Vincent's Hospital

Melbourne, Victoria, Australia

Site Status: RECRUITING

Countries

Australia

Central Contacts

Gareth Burns, MD

Role: CONTACT

gareth.burns@svha.org.au

+61309231 3581

Facility Contacts

Gareth Burns, MD

Role: primary

gareth.burns@svha.org.au

+61392313581

John Gough, RN

Role: backup

john.gough@svha.org.au

+61392313518

References

Hume SJ, Hall S, Burns G, Vogrin S, Tassone D, Desmond P, Ratnam D, Levy MT, Sawhney R, Nicoll A, Valaydon Z, Strasser SI, Ngu M, Sinclair M, Meredith C, Matthews GV, Visvanathan K, Holmes JA, Thompson AJ. Long-Term Follow-Up of Patients in a Prospective Study of NA Discontinuation Identifies Different Patterns of HBsAg Loss. Aliment Pharmacol Ther. 2025 Aug 21. doi: 10.1111/apt.70332. Online ahead of print.

Reference Type: DERIVED

PMID: 40842267 (View on PubMed)

Other Identifiers

032/14 Protocol # :APP106653

Identifier Type: -

Identifier Source: org_study_id