Chronic Hepatitis BPhase 4NCT01491295
Switch to Tenofovir Versus Continue Lamivudine/Adefovir Treatment in Lamivudine-resistance Chronic Hepatitis B Patients
A Phase 4 study testing Tenofovir disoproxil fumarate and Lamivudine plus adefovir in people with Chronic Hepatitis B, run by Taipei Veterans General Hospital, Taiwan at 1 site in Taiwan.
Trial summary
1. Adefovir add-on therapy is superior to switching to adefovir monotherapy or entecavir 1mg monotherapy for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R) 2. Long-term adefovir add-on therapy was effective for viral suppression. 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?
- Tenofovir disoproxil fumarate and Lamivudine plus adefovir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteTaiwan
- Study dates
- Sep 2012to Dec 2019
- 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
- HBsAg-positive for more than 6 months (HBeAg-positive or HBeAg-negative).
- Age > 20 y/o.
- Under lamivudine/adefovir treatment for more than 1 year due to previous lamivudine resistance (LAM-R), current HBV DNA is undetectable (< 20 IU/ml) during enrollment.
Who cannot join
- HCV, HIV, HDV coinfection.
- Uncontrolled HCC, malignancy or decompensated liver cirrhosis (CTP score ≥ 7).
- Uremia patients or Creatinine ≥ 2 mg/dl.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Taipei Veterans General Hospital-Division of Gastroenterology
Taipei, 11217
Yi-Hsiang Huang, 886-28712121 ext. 3055, yhhuang@vghtpe.gov.tw
Yi-Hsiang Huang
About this study
Official title: Randomized Trial of Switch to Tenofovir Versus Continue Lamivudine/Adefovir Treatment in Lamivudine-resistance Chronic Hepatitis B Patients Who Have Undergone Lamivudine/Adefovir Add-on Treatment
- Adefovir add-on therapy is superior to switching to adefovir monotherapy or entecavir 1mg monotherapy for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R)
- Long-term adefovir add-on therapy was effective for viral suppression. However, the economic burden for such dual antiviral therapy is heavy because of infinite treatment.
- Tenofovir disoproxil fumarate (TDF) is a potent antiviral agent. TDF demonstrated potent antiviral efficacy in a subset of lamivudine experienced HBeAg-positive patients. TDF is also superior to ADV in HBeAg-negative and HBeAg-positive treatment-naive patients.
- Theoretically, TDF can replace LAM/ADV when viral suppression has been achieved by LAM/ADV combination treatment in LAM-R CHB patients.
Read the detailed description
Hepatitis B virus (HBV) is a partially double-stranded DNA virus. HBV infection can induce a spectrum of disease ranging from asymptomatic infection to severe chronic liver diseases, including cirrhosis and hepatocellular carcinoma (HCC). Chronic HBV infection is also a major cause of HCC in Taiwan. Over 350 millions people worldwide are chronically infected with HBV. Lamivudine was the first marketing and is the first-line oral anti-viral agent for the therapy of chronic hepatitis B. Infinite nucleoside analogue therapy may be needed for long-term viral suppression especially in patients with HBeAg-negative chronic hepatitis B. The initial randomized studies demonstrated the clinical benefit and safety of lamivudine in both hepatitis B e antigen (HBeAg)-positive and -negative chronic hepatitis B patients. But as high as 20% of the cases under 1-year lamivudine treatment developed genotypic resistance, which defined as the presence of YMDD mutation on the HBV polymerase region. Genotypic resistance is almost always associated with virological breakthrough and exacerbation of liver function. Long-term lamivudine therapy was reported increase HBeAg seroconversion and provided clinical improvement in ALT levels. However, in a four-year follow-up study, YMDD-variant HBV was detected in as high as 67% of patients under lamivudine treatment. Several clinical studies have proven that adefovir add-on therapy is superior to switching to adefovir monotherapy or entecavir 1mg monotherapy for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R). Currently, AASLD and EASL guidelines recommend adefovir add-on therapy as a standard treatment for LAM-R CHB patients. Long-term adefovir add-on therapy was effective for viral suppression (8). However, the economic burden for such dual antiviral therapy is heavy because of infinite treatment.
Tenofovir disoproxil fumarate (TDF) is a potent antiviral agent. TDF and ETV are recommended oral first-line therapies for CHB. TDF demonstrated potent antiviral efficacy in a subset of lamivudine experienced HBeAg-positive patients. TDF is also superior to ADV in HBeAg-negative and HBeAg-positive treatment-naive patients. Theoretically, TDF can replace LAM/ADV when viral suppression has been achieved by LAM/ADV combination treatment in LAM-R CHB patients. This clinical trial is a proof of concept study to evaluate the efficacy of switching to TDF monotherapy in such patients.
- Conditions
- Chronic Hepatitis B
- Being tested
- Tenofovir disoproxil fumarate, Lamivudine plus adefovir
- Keywords
- Lamivudine, adefovir add on treatment, tenofovir, chronic hepatitis B
- 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.
Tenofovir disoproxil fumarateDrug
Also called Viread
Tenofovir disoproxil fumarate 300mg QD for 36 months (adjust dosage according to renal function)
Lamivudine plus adefovirDrug
Also called Zeffix, Hepsera
Lamivudine 100mg QD for 36 months (adjust dosage according to renal function) Adefovir 10mg QD for 36 months (adjust dosage according to renal function)
| Study group | Role | What they receive |
|---|---|---|
| Lamivudine plus adefovir | Active comparator | Continue lamivudine/adefovir add on treatment (standard treatment) Receives: Drug: Lamivudine plus adefovir |
| Tenofovir | Experimental | Switch from lamivudine/adefovir add on threatment to tenofovir monotherapy Receives: Drug: Tenofovir disoproxil fumarate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of virological breakthrough (defined as HBV DNA > 100 IU/ml)
Measured: Sustained viral suppression after switching to TDF for 36 months
Secondary outcomes (2)
HBeAg seroconversion (for HBeAg-positive patients)
Measured: HBeAg seroconversion rate at 1, 2 and 3 years
Incidence of HBsAg loss
Measured: Incidence of HBsAg loss at 1-, 2-, and 3 -years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2011 (estimated)
- Study startSep 2012
- Primary completionDec 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Taipei Veterans General Hospital, Taiwan
- Sponsor type
- Other government
- Collaborators
- Kaohsiung Medical University Chung-Ho Memorial Hospital, China Medical University Hospital, Chi Mei Medical Hospital, Chiayi Christian Hospital
- Responsible party
- Principal investigator, vghtpe user, Taipei Veterans General Hospital, Taiwan
- Investigators
- Yi-Hsiang Huang, Principal investigator, Taipei Veterans General Hospital, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01491295
- Sponsor's protocol ID
- IN-US-174-0194
- Status last verified
- Mar 2016
- First submitted
- 27 Oct 2011
- Last updated
- 1 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Switch to Tenofovir Versus Continue Lamivudine/Adefovir Treatment in Lamivudine-resistance Chronic Hepatitis B Patients Who Have Undergone Lamivudine/Adefovir Add-on Treatment
- ClinicalTrials.gov ID
- NCT01491295
- Acronym / sponsor ID
- IN-US-174-0194
- Conditions
- Chronic Hepatitis B
- Keywords
- Lamivudine, adefovir add on treatment, tenofovir, chronic hepatitis B
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Taipei Veterans General Hospital, TaiwanOther government
- Collaborators
- Kaohsiung Medical University Chung-Ho Memorial Hospital, China Medical University Hospital, Chi Mei Medical Hospital, Chiayi Christian Hospital
- Study start
- Sep 2012
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 13 Dec 2011 (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.
- Adefovir add-on therapy is superior to switching to adefovir monotherapy or entecavir 1mg monotherapy for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R)
- Long-term adefovir add-on therapy was effective for viral suppression. However, the economic burden for such dual antiviral therapy is heavy because of infinite treatment.
- Tenofovir disoproxil fumarate (TDF) is a potent antiviral agent. TDF demonstrated potent antiviral efficacy in a subset of lamivudine experienced HBeAg-positive patients. TDF is also superior to ADV in HBeAg-negative and HBeAg-positive treatment-naive patients.
- Theoretically, TDF can replace LAM/ADV when viral suppression has been achieved by LAM/ADV combination treatment in LAM-R CHB patients.
Detailed description
Hepatitis B virus (HBV) is a partially double-stranded DNA virus. HBV infection can induce a spectrum of disease ranging from asymptomatic infection to severe chronic liver diseases, including cirrhosis and hepatocellular carcinoma (HCC). Chronic HBV infection is also a major cause of HCC in Taiwan. Over 350 millions people worldwide are chronically infected with HBV. Lamivudine was the first marketing and is the first-line oral anti-viral agent for the therapy of chronic hepatitis B. Infinite nucleoside analogue therapy may be needed for long-term viral suppression especially in patients with HBeAg-negative chronic hepatitis B. The initial randomized studies demonstrated the clinical benefit and safety of lamivudine in both hepatitis B e antigen (HBeAg)-positive and -negative chronic hepatitis B patients. But as high as 20% of the cases under 1-year lamivudine treatment developed genotypic resistance, which defined as the presence of YMDD mutation on the HBV polymerase region. Genotypic resistance is almost always associated with virological breakthrough and exacerbation of liver function. Long-term lamivudine therapy was reported increase HBeAg seroconversion and provided clinical improvement in ALT levels. However, in a four-year follow-up study, YMDD-variant HBV was detected in as high as 67% of patients under lamivudine treatment. Several clinical studies have proven that adefovir add-on therapy is superior to switching to adefovir monotherapy or entecavir 1mg monotherapy for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R). Currently, AASLD and EASL guidelines recommend adefovir add-on therapy as a standard treatment for LAM-R CHB patients. Long-term adefovir add-on therapy was effective for viral suppression (8). However, the economic burden for such dual antiviral therapy is heavy because of infinite treatment.
Tenofovir disoproxil fumarate (TDF) is a potent antiviral agent. TDF and ETV are recommended oral first-line therapies for CHB. TDF demonstrated potent antiviral efficacy in a subset of lamivudine experienced HBeAg-positive patients. TDF is also superior to ADV in HBeAg-negative and HBeAg-positive treatment-naive patients. Theoretically, TDF can replace LAM/ADV when viral suppression has been achieved by LAM/ADV combination treatment in LAM-R CHB patients. This clinical trial is a proof of concept study to evaluate the efficacy of switching to TDF monotherapy in such patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lamivudine plus adefovir | Active comparator | Drug: Lamivudine plus adefovirContinue lamivudine/adefovir add on treatment (standard treatment) |
| Tenofovir | Experimental | Drug: Tenofovir disoproxil fumarateSwitch from lamivudine/adefovir add on threatment to tenofovir monotherapy |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- HBsAg-positive for more than 6 months (HBeAg-positive or HBeAg-negative).
- Age > 20 y/o.
- Under lamivudine/adefovir treatment for more than 1 year due to previous lamivudine resistance (LAM-R), current HBV DNA is undetectable (< 20 IU/ml) during enrollment.
Key exclusion criteria (3 listed)
- HCV, HIV, HDV coinfection.
- Uncontrolled HCC, malignancy or decompensated liver cirrhosis (CTP score ≥ 7).
- Uremia patients or Creatinine ≥ 2 mg/dl.
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 |
|---|---|---|
| Tenofovir disoproxil fumarateAlso: VireadTenofovir disoproxil fumarate 300mg QD for 36 months (adjust dosage according to renal function) | Drug | Tenofovir |
| Lamivudine plus adefovirAlso: Zeffix, HepseraLamivudine 100mg QD for 36 months (adjust dosage according to renal function) Adefovir 10mg QD for 36 months (adjust dosage according to renal function) | Drug | Lamivudine plus adefovir |
Primary outcome
Incidence of virological breakthrough (defined as HBV DNA > 100 IU/ml)
Time frame: Sustained viral suppression after switching to TDF for 36 months
2 secondary outcomes
HBeAg seroconversion (for HBeAg-positive patients)
Time frame: HBeAg seroconversion rate at 1, 2 and 3 years
Incidence of HBsAg loss
Time frame: Incidence of HBsAg loss at 1-, 2-, and 3 -years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2016.
Related trials for Chronic Hepatitis B
Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B
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.
Yi-Hsiang Huang principal investigator
Taipei Veterans General Hospital, Taiwan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tenofovir disoproxil fumarate and Lamivudine plus adefovir in people with Chronic Hepatitis B, run by Taipei Veterans General Hospital, Taiwan at 1 site in 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 3 inclusion and 3 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 1 Apr 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 Taiwan. 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.
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, MD, PhD (886-2-28712121 ext. 3055, yhhuang@vghtpe.gov.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of virological breakthrough (defined as HBV DNA > 100 IU/ml) (time frame: Sustained viral suppression after switching to TDF for 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Apr 2016.