Hepatitis B, ChronicPhase 4NCT00823550
Antiviral Therapy in Hepatitis B Virus (HBV)-Related Advanced Liver Disease Patients
A Phase 4 study testing Entecavir and Lamivudine in people with Hepatitis B, Chronic, run by Yonsei University at 1 site in South Korea.
Trial summary
This is a randomized, open label, phase IV, multicenter study for efficacy and safety of lamivudine versus entecarvir therapy in HBV-related advanced liver disease patients with high viral load and normal or slightly elevated transaminase. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- Entecavir and Lamivudine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 462 participants
- Where
- 1 siteSouth Korea
- Study dates
- Jan 2009to Jul 2015
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female, 18 years of age or older
- HBsAg positive for more than 6 months
- Serum HBV DNA > 2,000 IU/ml
- Serum ALT < 2 X ULN on two consecutive occasions at least 3 months apart
- Naïve to nucleoside or nucleotide therapy
- On liver biopsy, fibrosis score ≥ 3 according to METAVIR scoring system (within 2 years of Day 0)
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- If liver biopsy is not available, subjects must have two of the following items
- Overt findings of cirrhosis by radiologic evidence (MRI, CT, US)
- Gastrointestinal varices
- Platelet count < 100,000,Splenomegaly (Spleen size - 12cm)
- The patient who is willing and able to provide written informed consent to participate in this study
Who cannot join
- A history of SBP, variceal bleeding, HEP, HCC
- Decompensated liver disease (Child-Pugh score > 10)
- Co-infected with HCV or HIV
- History of any other forms of liver disease.
- Patient who is pregnant or breastfeeding
- Treatment with immunosuppressive, immunomodulatory agents or antiviral agents within 6 months prior to study entry
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- A history of liver transplantation or planned for liver transplantation
- A history of any other medical disease or condition that would make the patients unsuitable for the study.
- Patient is currently abusing alcohol or illicit drugs or has a history of alcohol abuse or illicit substance abuse within the preceding 2 years.
- Patient is enrolled or plans to enroll in another clinical trial of an investigational agent while participating in this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Open Label, Phase IV, Multicenter Study for Efficacy and Safety of Lamivudine Versus Entecarvir Therapy in HBV-related Advanced Liver Disease Patients With High Viral Load and Normal or Slightly Elevated Transaminase
This is a randomized, open label, phase IV, multicenter study for efficacy and safety of lamivudine versus entecarvir therapy in HBV-related advanced liver disease patients with high viral load and normal or slightly elevated transaminase.
Read the detailed description
Currently, treatment guidelines for the management of chronic hepatitis B (CHB) recommend that patients with serum HBV DNA > 105 copies/ml and elevated ALT levels greater than two times the upper limit of normal (ULN) are obvious candidates for antiviral therapy. Guidelines also suggest that antiviral therapy be considered in CHB patients with high viral load, if a biopsy shows significant liver disease despite ALT ≤ 2× ULN. Data from recent trials in hepatitis B patients who present with normal to minimally elevated ALT (≤ 2× ULN) indicate that significant hepatic pathology could still be found. Serum ALT level may not accurately predict activity of liver damage. ALT is a poor predictor of outcome and therefore is not a suitable criterion for antiviral therapy in chronic hepatitis B infection. Also, a recent large randomized controlled clinical trial comparing lamivudine maintenance and placebo in advanced fibrosis (Ishak fibrosis score ≥ 4) suggests that sustained viral suppression with antiviral therapy is linked to reduced risk for disease progression. (Liaw YF et al. NEJM 2004;351:1521-1531)
- Conditions
- Hepatitis B, Chronic
- Being tested
- Entecavir, Lamivudine
- Keywords
- Chronic hepatitis B, Advanced fibrosis, Lamivudine, 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.
EntecavirDrug
Also called Baraclude 0.5mg
entecavir 0.5 mg QD
LamivudineDrug
Also called Zeffix 100mg
lamivudine 100 mg QD
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | entecavir 0.5 mg QD Receives: Drug: Entecavir |
| B | Active comparator | lamivudine 100 mg QD Receives: Drug: Lamivudine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to disease progression as defined by the first occurrence of any of the cirrhosis compolications
Measured: 5 years
Secondary outcomes (1)
Proportion of patients achieving either HBV DNA level ≤ 60 IU/mL Proportion of patients with ALT normalization Proportion of patients with HBeAg loss and seronconversion Proportion of patients with virologic breakthrough
Measured: at months 12, 24, 36, 48, and 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2009 (estimated)
- Study startJan 2009
- Primary completionJul 2014 (estimated)
- Study completionJul 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe 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
- 462 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Collaborators
- Severance Hospital, Kangbuk Samsung Hospital, Konkuk University Hospital, Chung-Ang University, Ajou University, Inha University Hospital, Soonchunhyang University Hospital, The Catholic University of Korea, Hallym University Medical Center, Kyungpook National University Hospital, Keimyung University, Korea University Anam Hospital, Korea University, Hanyang University, Inje University, Pusan National University Hospital, Bristol-Myers Squibb
- Investigators
- Kwnag-Hyub Han, MD, Study chair, Yonsei Univsersity College of MedicineJun Yong Park, MD, Study director, Yonsei Univsersity College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00823550
- Sponsor's protocol ID
- 4-2008-0296
- Status last verified
- Jan 2009
- First submitted
- 14 Jan 2009
- Last updated
- 16 Dec 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open Label, Phase IV, Multicenter Study for Efficacy and Safety of Lamivudine Versus Entecarvir Therapy in HBV-related Advanced Liver Disease Patients With High Viral Load and Normal or Slightly Elevated Transaminase
- ClinicalTrials.gov ID
- NCT00823550
- Acronym / sponsor ID
- 4-2008-0296
- Conditions
- Hepatitis B, Chronic
- Keywords
- Chronic hepatitis B, Advanced fibrosis, Lamivudine, Entecavir
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 462 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Collaborators
- Severance Hospital, Kangbuk Samsung Hospital, Konkuk University Hospital, Chung-Ang University, Ajou University, Inha University Hospital, Soonchunhyang University Hospital, The Catholic University of Korea, Hallym University Medical Center, Kyungpook National University Hospital, Keimyung University, Korea University Anam Hospital, Korea University, Hanyang University, Inje University, Pusan National University Hospital, Bristol-Myers Squibb
- Study start
- Jan 2009
- Primary completion
- Jul 2014 (estimated)
- Study completion
- Jul 2015 (estimated)
- First posted
- 15 Jan 2009 (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.
This is a randomized, open label, phase IV, multicenter study for efficacy and safety of lamivudine versus entecarvir therapy in HBV-related advanced liver disease patients with high viral load and normal or slightly elevated transaminase.
Detailed description
Currently, treatment guidelines for the management of chronic hepatitis B (CHB) recommend that patients with serum HBV DNA > 105 copies/ml and elevated ALT levels greater than two times the upper limit of normal (ULN) are obvious candidates for antiviral therapy. Guidelines also suggest that antiviral therapy be considered in CHB patients with high viral load, if a biopsy shows significant liver disease despite ALT ≤ 2× ULN. Data from recent trials in hepatitis B patients who present with normal to minimally elevated ALT (≤ 2× ULN) indicate that significant hepatic pathology could still be found. Serum ALT level may not accurately predict activity of liver damage. ALT is a poor predictor of outcome and therefore is not a suitable criterion for antiviral therapy in chronic hepatitis B infection. Also, a recent large randomized controlled clinical trial comparing lamivudine maintenance and placebo in advanced fibrosis (Ishak fibrosis score ≥ 4) suggests that sustained viral suppression with antiviral therapy is linked to reduced risk for disease progression. (Liaw YF et al. NEJM 2004;351:1521-1531)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Entecavirentecavir 0.5 mg QD |
| B | Active comparator | Drug: Lamivudinelamivudine 100 mg QD |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male and female, 18 years of age or older
- HBsAg positive for more than 6 months
- Serum HBV DNA > 2,000 IU/ml
- Serum ALT < 2 X ULN on two consecutive occasions at least 3 months apart
- Naïve to nucleoside or nucleotide therapy
Key exclusion criteria (10 listed)
- A history of SBP, variceal bleeding, HEP, HCC
- Decompensated liver disease (Child-Pugh score > 10)
- Co-infected with HCV or HIV
- History of any other forms of liver disease.
- Patient who is pregnant or breastfeeding
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 |
|---|---|---|
| EntecavirAlso: Baraclude 0.5mgentecavir 0.5 mg QD | Drug | A |
| LamivudineAlso: Zeffix 100mglamivudine 100 mg QD | Drug | B |
Primary outcome
Time to disease progression as defined by the first occurrence of any of the cirrhosis compolications
Time frame: 5 years
1 secondary outcome
Proportion of patients achieving either HBV DNA level ≤ 60 IU/mL Proportion of patients with ALT normalization Proportion of patients with HBeAg loss and seronconversion Proportion of patients with virologic breakthrough
Time frame: at months 12, 24, 36, 48, and 60
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2010.
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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.
Kwnag-Hyub Han, MD study chair
Yonsei Univsersity College of Medicine
Jun Yong Park, MD study director
Yonsei Univsersity College of Medicine
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 Entecavir and Lamivudine in people with Hepatitis B, Chronic, run by Yonsei University at 1 site in South Korea.
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 11 inclusion and 10 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 16 Dec 2010. 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 South Korea. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to disease progression as defined by the first occurrence of any of the cirrhosis compolications (time frame: 5 years). 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 16 Dec 2010.