Chronic Hepatitis BPhase 4NCT03308890
The Effect of Entecavir Consolidation on Post-TDF Treatment Durability
A Phase 4 study testing 0.5mg Baraclude(entecavir) in people with Chronic Hepatitis B, run by Taipei Veterans General Hospital, Taiwan.
Trial summary
Clinical relapse occurred much earlier and tended to be more severe after cessation of TDF than ETV. The follow-up interval and intensity would be different between ETV and TDF after discontinuation of therapy. Whether switch therapy from TDF to ETV can modify the pattern of relapse is interesting but unclear. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- 0.5mg Baraclude(entecavir)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2017to 30 Apr 2022
- Phase
- Phase 4
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >20 yrs old.
- No history of Lamivudine or telbivudine resistance.
- HBsAg positive for more than 6 months.
- HBeAg (-).
- HBeAg-negative CHB under TDF treatment for mora than 2 years and fulfilled APASL 2012 guideline's stopping rule: HBeAg (-): undetectable HBV DNA on 3 separate occasions at least 6 months apart.
Who cannot join
- Lamivudine/telbivudine resistance.
- HBeAg (+).
- HIV, HCV co-infection.
- Under immunosuppressant treatment (including steroid and biologics).
Trial locations and contacts
No sites are listed yet.
About this study
Clinical relapse occurred much earlier and tended to be more severe after cessation of TDF than ETV. The follow-up interval and intensity would be different between ETV and TDF after discontinuation of therapy. Whether switch therapy from TDF to ETV can modify the pattern of relapse is interesting but unclear. Our hypothesis is that entecavir consolidation on post-TDF treatment patients reduce and delay the clinical relapse effectively. Hence in this proof of concept study we would like to evaluate the effect of 6 months and 12 months of entecavir consolidation on post-TDF treatment durability.
Read the detailed description
Long term nucleoside/nucleotide analogues (NAs) treatment is required in the treatment of chronic hepatitis B (CHB). According to current treatment guidelines from APASL 2015, NAs treatment can be stopped if, after HBsAg loss following either anti-HBs seroconversion or at least 12 months of a post-HBsAg clearance consolidation period or after treatment for at least 2 years with undetectable HBV DNA documented on three separate occasions, 6 months apart. In Taiwan, the National Health Insurance system only reimburse 3 years NAs for CHB patients. Previous study from Jeng et al. suggested that the 1-year rate of clinical relapse (HBV DNA>2,000 IU/mL plus ALT>2X ULN) after cessation of entecavir(ETV) therapy by APASL stopping rule (treatment >2 years, HBV DNA undetectable >1 year) in HBeAg-negative chronic hepatitis B(CHB) patients was 45%, of which 25.6% occurred within 6 months. Recently, another study from Jeng et al showed that 34 HBeAg(-) patients who stopped TDF therapy by APASL stopping rule were followed-up every 1-3 months for >6 months. Of these 34 patients, mean age was 51.8 years, 82.4% were males and 14(41.2%) were cirrhotic. The 1-year cumulative clinical relapse rate was 46%, of which 93.3% occurred within 6 months, and 13.3% developed decompensation. Clinical relapse occurred much earlier and tended to be more severe after cessation of TDF than ETV. The follow-up interval and intensity would be different between ETV and TDF after discontinuation of therapy. Whether switch therapy from TDF to ETV can modify the pattern of relapse is interesting but unclear. Our hypothesis is that entecavir consolidation on post-TDF treatment patients reduce and delay the clinical relapse effectively. Hence in this proof of concept study we would like to evaluate the effect of 6 months and 12 months of entecavir consolidation on post-TDF treatment durability.
- Conditions
- Chronic Hepatitis B
- Being tested
- 0.5mg Baraclude(entecavir)
- 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.
0.5mg Baraclude(entecavir)Drug
0.5mg Baraclude (entecavir) QD for 6 months after cessation of TDF.
0.5mg Baraclude(entecavir)Drug
0.5mg Baraclude (entecavir) QD for 12 month after cessation of TDF.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Active comparator | 0.5mg Entecavir QD for 6 months after cessation of TDF and clinical observation for up to 6 months after the end of study follow-up. Receives: Drug: 0.5mg Baraclude(entecavir) |
| Arm 2 | Active comparator | 0.5mg Entecavir QD for 12 months after cessation of TDF and clinical observation for up to 6 months after the end of study follow-up. Receives: Drug: 0.5mg Baraclude(entecavir) |
| Arm 3 | No intervention | No consolidation arm and observation only and clinical observation for up to 6 months after the end of study follow-up. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical relapse rate.
Clinical relapse rate (HBV DNA>2000 IU/ml and ALT> 2x ULN) within 6 months after cessation of TDF or ETV consolidation treatment (up to 6 or 12 months on post-TDF therapy).
Measured: Up to 24 months.
Secondary outcomes (3)
Severity of ATL flare
Severity of ATL flare (ALT>5X and 10X) within 6 months after cessation of TDF or ETV consolidation treatment (up to 6 or 12 months on post-TDF therapy).
Measured: Up to 24 months.
Liver decompensation incidence
Liver decompensation incidence (Total bilirubin > 2mg/dl and/or PT prolongation> 3 sec) within 6 months after cessation of TDF or ETV consolidation treatment (up to 6 or 12 months on post-TDF therapy).
Measured: Up to 24 months.
Renal function changes
Renal function changes based on eGFR (monitor per 3m) within 6 months after cessation of TDF or ETV consolidation treatment (up to 6 or 12 months on post-TDF therapy).
Measured: Up to 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2017
- Study start1 Nov 2017 (estimated)
- Primary completion1 Jul 2019 (estimated)
- Study completion30 Apr 2022 (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 BStudies of the same condition, open and under way.
- More trials run by Taipei Veterans General Hospital, TaiwanThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Arm 1：0.5mg Entecavir QD for 6 months after cessation of TDF. Arm 2：0.5mg Entecavir QD for 12 months after cessation of TDF. Arm 3：No consolidation arm and observation only. Clinical observation for up to 6 months after the end of study follow-up for all arms.
- Masking
- None (open label)
- Enrolment
- 156 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Taipei Veterans General Hospital, Taiwan
- Sponsor type
- Other government
- Collaborators
- China Medical University Hospital, Chang Gung Memorial Hospital, Changhua Christian Hospital
- Responsible party
- Principal investigator, vghtpe user, Taipei Veterans General Hospital, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03308890
- Sponsor's protocol ID
- AI463-527
- Status last verified
- Oct 2017
- First submitted
- 5 Oct 2017
- Last updated
- 17 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016 Jan;10(1):1-98. doi: 10.1007/s12072-015-9675-4. Epub 2015 Nov 13.
PubMed 26563120Jeng WJ, Sheen IS, Chen YC, Hsu CW, Chien RN, Chu CM, Liaw YF. Off-therapy durability of response to entecavir therapy in hepatitis B e antigen-negative chronic hepatitis B patients. Hepatology. 2013 Dec;58(6):1888-96. doi: 10.1002/hep.26549. Epub 2013 Oct 17.
PubMed 23744454Jeng WJ, Chen YC, Sheen IS, Lin CL, Hu TH, Chien RN, Liaw YF. Clinical Relapse After Cessation of Tenofovir Therapy in Hepatitis B e Antigen-Negative Patients. Clin Gastroenterol Hepatol. 2016 Dec;14(12):1813-1820.e1. doi: 10.1016/j.cgh.2016.07.002. Epub 2016 Jul 9.
PubMed 27404969
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Entecavir Consolidation on Post-TDF Treatment Durability
- ClinicalTrials.gov ID
- NCT03308890
- Acronym / sponsor ID
- AI463-527
- Conditions
- Chronic Hepatitis B
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 156 participants (estimated)
- Lead sponsor
- Taipei Veterans General Hospital, TaiwanOther government
- Collaborators
- China Medical University Hospital, Chang Gung Memorial Hospital, Changhua Christian Hospital
- Study start
- 1 Nov 2017 (estimated)
- Primary completion
- 1 Jul 2019 (estimated)
- Study completion
- 30 Apr 2022 (estimated)
- First posted
- 13 Oct 2017 (actual)
- 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.
Clinical relapse occurred much earlier and tended to be more severe after cessation of TDF than ETV. The follow-up interval and intensity would be different between ETV and TDF after discontinuation of therapy. Whether switch therapy from TDF to ETV can modify the pattern of relapse is interesting but unclear. Our hypothesis is that entecavir consolidation on post-TDF treatment patients reduce and delay the clinical relapse effectively. Hence in this proof of concept study we would like to evaluate the effect of 6 months and 12 months of entecavir consolidation on post-TDF treatment durability.
Detailed description
Long term nucleoside/nucleotide analogues (NAs) treatment is required in the treatment of chronic hepatitis B (CHB). According to current treatment guidelines from APASL 2015, NAs treatment can be stopped if, after HBsAg loss following either anti-HBs seroconversion or at least 12 months of a post-HBsAg clearance consolidation period or after treatment for at least 2 years with undetectable HBV DNA documented on three separate occasions, 6 months apart. In Taiwan, the National Health Insurance system only reimburse 3 years NAs for CHB patients. Previous study from Jeng et al. suggested that the 1-year rate of clinical relapse (HBV DNA>2,000 IU/mL plus ALT>2X ULN) after cessation of entecavir(ETV) therapy by APASL stopping rule (treatment >2 years, HBV DNA undetectable >1 year) in HBeAg-negative chronic hepatitis B(CHB) patients was 45%, of which 25.6% occurred within 6 months. Recently, another study from Jeng et al showed that 34 HBeAg(-) patients who stopped TDF therapy by APASL stopping rule were followed-up every 1-3 months for >6 months. Of these 34 patients, mean age was 51.8 years, 82.4% were males and 14(41.2%) were cirrhotic. The 1-year cumulative clinical relapse rate was 46%, of which 93.3% occurred within 6 months, and 13.3% developed decompensation. Clinical relapse occurred much earlier and tended to be more severe after cessation of TDF than ETV. The follow-up interval and intensity would be different between ETV and TDF after discontinuation of therapy. Whether switch therapy from TDF to ETV can modify the pattern of relapse is interesting but unclear. Our hypothesis is that entecavir consolidation on post-TDF treatment patients reduce and delay the clinical relapse effectively. Hence in this proof of concept study we would like to evaluate the effect of 6 months and 12 months of entecavir consolidation on post-TDF treatment durability.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Arm 1：0.5mg Entecavir QD for 6 months after cessation of TDF. Arm 2：0.5mg Entecavir QD for 12 months after cessation of TDF. Arm 3：No consolidation arm and observation only. Clinical observation for up to 6 months after the end of study follow-up for all arms.
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Active comparator | Drug: 0.5mg Baraclude(entecavir)0.5mg Entecavir QD for 6 months after cessation of TDF and clinical observation for up to 6 months after the end of study follow-up. |
| Arm 2 | Active comparator | Drug: 0.5mg Baraclude(entecavir)0.5mg Entecavir QD for 12 months after cessation of TDF and clinical observation for up to 6 months after the end of study follow-up. |
| Arm 3 | No intervention | –No consolidation arm and observation only and clinical observation for up to 6 months after the end of study follow-up. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- >20 yrs old.
- No history of Lamivudine or telbivudine resistance.
- HBsAg positive for more than 6 months.
- HBeAg (-).
- HBeAg-negative CHB under TDF treatment for mora than 2 years and fulfilled APASL 2012 guideline's stopping rule: HBeAg (-): undetectable HBV DNA on 3 separate occasions at least 6 months apart.
Key exclusion criteria (4 listed)
- Lamivudine/telbivudine resistance.
- HBeAg (+).
- HIV, HCV co-infection.
- Under immunosuppressant treatment (including steroid and biologics).
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 |
|---|---|---|
| 0.5mg Baraclude(entecavir)0.5mg Baraclude (entecavir) QD for 6 months after cessation of TDF. | Drug | Arm 1 |
| 0.5mg Baraclude(entecavir)0.5mg Baraclude (entecavir) QD for 12 month after cessation of TDF. | Drug | Arm 2 |
Primary outcome
Clinical relapse rate.
Time frame: Up to 24 months.
Clinical relapse rate (HBV DNA>2000 IU/ml and ALT> 2x ULN) within 6 months after cessation of TDF or ETV consolidation treatment (up to 6 or 12 months on post-TDF therapy).
3 secondary outcomes
Severity of ATL flare
Time frame: Up to 24 months.
Liver decompensation incidence
Time frame: Up to 24 months.
Renal function changes
Time frame: Up to 24 months.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2017.
- Background: PubMed 26563120Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016 Jan;10(1):1-98. doi: 10.1007/s12072-015-9675-4. Epub 2015 Nov 13.
- Background: PubMed 23744454Jeng WJ, Sheen IS, Chen YC, Hsu CW, Chien RN, Chu CM, Liaw YF. Off-therapy durability of response to entecavir therapy in hepatitis B e antigen-negative chronic hepatitis B patients. Hepatology. 2013 Dec;58(6):1888-96. doi: 10.1002/hep.26549. Epub 2013 Oct 17.
- Background: PubMed 27404969Jeng WJ, Chen YC, Sheen IS, Lin CL, Hu TH, Chien RN, Liaw YF. Clinical Relapse After Cessation of Tenofovir Therapy in Hepatitis B e Antigen-Negative Patients. Clin Gastroenterol Hepatol. 2016 Dec;14(12):1813-1820.e1. doi: 10.1016/j.cgh.2016.07.002. Epub 2016 Jul 9.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing 0.5mg Baraclude(entecavir) in people with Chronic Hepatitis B, run by Taipei Veterans General Hospital, Taiwan.
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 5 inclusion and 4 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 17 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Yi-Hsiang Huang, M.D. Ph.D. (+886-2-28757506, yhhuang@vghtpe.gov.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical relapse rate. (time frame: Up to 24 months.). 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 NCT03308890, 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 17 Oct 2017.