Chronic Hepatitis B.STOPNCT02581033
Determinants of Virological Response After Discontinuation of Nucleoside Analogue Therapy in Hepatitis B Patients
A study testing Nucleoside Analogue therapy in people with Chronic Hepatitis B., run by St Vincent's Hospital Melbourne at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Chronic Hepatitis B.
- What is being tested?
- Nucleoside Analogue therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteAustralia
- Study dates
- May 2014to May 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Australia1 site, 1 recruiting
- Recruiting
St Vincent's Hospital
Melbourne, Victoria, 3065
Gareth Burns, MD, +61392313581, gareth.burns@svha.org.au
John Gough, RN, +61392313518, john.gough@svha.org.au
About this study
Official title: 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.
Read the 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.
- Being tested
- Nucleoside Analogue therapy
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nucleoside Analogue therapyDrug
Also called Cessation of Nucleoside Analogue Therapy
Determinants of sustained virological response after discontinuation of long-term nucleoside analogue therapy in chronic hepatitis B patients.
| Study group | Role | What they receive |
|---|---|---|
| Nucleoside analogue therapy cessation | Experimental | To determine if a sustained virological response can be achieved after discontinuation of long-term nucleoside analogue therapy in chronic hepatitis B patients. Receives: Drug: Nucleoside Analogue therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 outcomes (1)
To identify novel immunological determinants of SVR, the assessment will be by serum assay.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2015 (estimated)
- Study startMay 2014
- Primary completionMay 2018 (estimated)
- Study completionMay 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis B.Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St Vincent's Hospital Melbourne
- Sponsor type
- University, hospital or other
- Collaborators
- National Health and Medical Research Council, Australia
- Responsible party
- Principal investigator, Alexander Thompson, St Vincent's Hospital Melbourne
- Investigators
- Alexander Thompson, MD, Principal investigator, St Vincent's Hospital Melbourne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02581033
- Sponsor's protocol ID
- 032/14 Protocol # :APP106653
- Acronym
- STOP
- Status last verified
- Oct 2016
- First submitted
- 15 Oct 2015
- Last updated
- 14 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Hume SJ, Visvanathan K, Cheng K, Jackson K, Vogrin S, Hall SAL, Burns GS, Desmond PV, Ratnam D, Levy MT, Sawhney R, Strasser SI, Ngu MC, Sinclair M, Meredith C, Matthews G, Valaydon Z, Wong D, Littlejohn M, Holmes JA, Revill PA, Thompson AJ, Warner N. Anti-HBs Immune Complex Levels: A Novel Marker of Hepatitis Flare Following Nucleos(t)ide Analog Withdrawal in HBeAg-negative Chronic Hepatitis B. J Infect Dis. 2026 Mar 17;233(3):e621-e629. doi: 10.1093/infdis/jiaf569.
PubMed 41239780Hume 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. 2026 Jan;63(2):231-241. doi: 10.1111/apt.70332. Epub 2025 Aug 21.
PubMed 40842267Hume SJ, Wong DK, Yuen MF, Jackson K, Bonanzinga S, Vogrin S, Hall SAL, Burns GS, Desmond PV, Sundararajan V, Ratnam D, Levy MT, Lubel JS, Nicoll AJ, Strasser SI, Sievert W, Ngu MC, Sinclair M, Meredith C, Matthews G, Revill PA, Littlejohn M, Bowden S, Visvanathan K, Holmes JA, Thompson AJ. High end-of-treatment hepatitis B core-related antigen levels predict hepatitis flare after stopping nucleot(s)ide analogue therapy. Liver Int. 2024 Oct;44(10):2605-2614. doi: 10.1111/liv.16029. Epub 2024 Jul 15.
PubMed 39007640
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determinants of Sustained Virological Response After Discontinuation of Long-term Nucleoside Analogue Therapy in Chronic Hepatitis B Patients
- ClinicalTrials.gov ID
- NCT02581033
- Acronym / sponsor ID
- STOP / 032/14 Protocol # :APP106653
- Conditions
- Chronic Hepatitis B.
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- St Vincent's Hospital MelbourneUniversity, hospital or other
- Collaborators
- National Health and Medical Research Council, Australia
- Study start
- May 2014
- Primary completion
- May 2018 (estimated)
- Study completion
- May 2018 (estimated)
- First posted
- 20 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nucleoside analogue therapy cessation | Experimental | Drug: Nucleoside Analogue therapyTo determine if a sustained virological response can be achieved after discontinuation of long-term nucleoside analogue therapy in chronic hepatitis B patients. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (17 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nucleoside Analogue therapyAlso: Cessation of Nucleoside Analogue TherapyDeterminants of sustained virological response after discontinuation of long-term nucleoside analogue therapy in chronic hepatitis B patients. | Drug | Nucleoside analogue therapy cessation |
Primary outcome
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.
1 secondary outcome
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2016.
- Derived from this study: PubMed 41239780Hume SJ, Visvanathan K, Cheng K, Jackson K, Vogrin S, Hall SAL, Burns GS, Desmond PV, Ratnam D, Levy MT, Sawhney R, Strasser SI, Ngu MC, Sinclair M, Meredith C, Matthews G, Valaydon Z, Wong D, Littlejohn M, Holmes JA, Revill PA, Thompson AJ, Warner N. Anti-HBs Immune Complex Levels: A Novel Marker of Hepatitis Flare Following Nucleos(t)ide Analog Withdrawal in HBeAg-negative Chronic Hepatitis B. J Infect Dis. 2026 Mar 17;233(3):e621-e629. doi: 10.1093/infdis/jiaf569.
- Derived from this study: PubMed 40842267Hume 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. 2026 Jan;63(2):231-241. doi: 10.1111/apt.70332. Epub 2025 Aug 21.
- Derived from this study: PubMed 39007640Hume SJ, Wong DK, Yuen MF, Jackson K, Bonanzinga S, Vogrin S, Hall SAL, Burns GS, Desmond PV, Sundararajan V, Ratnam D, Levy MT, Lubel JS, Nicoll AJ, Strasser SI, Sievert W, Ngu MC, Sinclair M, Meredith C, Matthews G, Revill PA, Littlejohn M, Bowden S, Visvanathan K, Holmes JA, Thompson AJ. High end-of-treatment hepatitis B core-related antigen levels predict hepatitis flare after stopping nucleot(s)ide analogue therapy. Liver Int. 2024 Oct;44(10):2605-2614. doi: 10.1111/liv.16029. Epub 2024 Jul 15.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexander Thompson, MD principal investigator
St Vincent's Hospital Melbourne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nucleoside Analogue therapy in people with Chronic Hepatitis B., run by St Vincent's Hospital Melbourne at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gareth Burns, MD (+61309231 3581, gareth.burns@svha.org.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02581033, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2016; AzTrials last refreshed its copy on 8 Nov 2026.