Hepatitis B Virus-Related Hepatocellular CarcinomaCTEAMNCT01957618
The Follow-up Study of Chronic Hepatitis B Patients With Liver Cirrhosis Receiving Anti-HBV Therapy
An observational study of Hepatitis B Virus-Related Hepatocellular Carcinoma, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
Hepatitis B virus (HBV) infection is a global health problem, especially in the endemic area like Taiwan, where there are more than 3 million chronic hepatitis B carriers. Patients with chronic HBV infection are at increased risk of developing cirrhosis, which may have disastrous complications, including hepatic… Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Hepatitis B Virus-Related Hepatocellular Carcinoma
- How many people
- 1,500 participants
- Where
- 1 siteTaiwan
- Study dates
- Oct 2011to Dec 2021
- Phase
- Observational
- 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
Study population: from hospitals
Who may be able to join
- Age older than 20 years old.
- HBsAg (+) > 6 months
- Baseline serum HBV DNA ≧ 2000 IU/mL (10,000 copies/mL)
- Liver cirrhosis (Child A) before or at enrollment, diagnosed by 1). Liver biopsy（Metavir F4 or Ishak > F5） or 2). Ultrasonographic evidence of cirrhosis with signs of portal hypertension (splenomegaly or presence of esophageal or gastric varices)
- Receiving long-term anti-HBV therapy
- Age older than 20 years old.
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- HBsAg (+) > 6 months
- Baseline serum HBV DNA ≧ 2000 IU/mL (10,000 copies/mL)
- Liver cirrhosis (Child A) before or at enrollment, diagnosed by 1). Liver biopsy（Metavir F4 or Ishak > F5） or 2). Ultrasonographic evidence of cirrhosis with signs of portal hypertension (splenomegaly or presence of esophageal or gastric varices)
- without receiving treatment
Who cannot join
- . Co-infection of HCV (anti-HCV (+)) or HIV
- . Alcoholism (alcohol consumption > 20 gm/day)
- . Serological evidence suggestive of autoimmune hepatitis, primary biliary cirrhosis, Wilson's disease and hemochromatosis
- . Liver decompensation (Child-Pugh classification of B or C)
- . Evidence of HCC at study entry
- . Pregnant women
Trial locations and contacts
1 site in 1 country.
About this study
Hepatitis B virus (HBV) infection is a global health problem, especially in the endemic area like Taiwan, where there are more than 3 million chronic hepatitis B carriers. Patients with chronic HBV infection are at increased risk of developing cirrhosis, which may have disastrous complications, including hepatic decompensation, and hepatocellular carcinoma (HCC). The liver cirrhosis related complications accounts for the 8th leading cause of deaths in Taiwan; whereas, the HCC is the 2nd leading cause of deaths among all cancers. Therefore, it is prudent to develop strategies to prevent or halt the progression of liver cirrhosis.
For HBV patients who have already had cirrhosis, the main treatment objective is to reduce their risk of complications. A large-scale multicenter clinical trial showed that viral suppression using lamivudine in patients with advanced fibrosis effectively decreases the risk of HCC and liver-related complications. This study highlights the importance to treat HBV-related cirrhosis patients; however, several issues remain to be addressed.
Read more
The first issue is that this clinical trial only enrolled patients with positive HBeAg or HBV-DNA level >1.4 x105 IU/mL. However, the current recommended threshold for cirrhotic patients to start anti-viral treatment is 2000 IU/mL. Whether anti-HBV therapy benefits cirrhotic patients in this level is still unclear. Second, lamivudine was used in this clinical trial; however, the high resistant rate of lamivudine during treatment probably lowers its protective effect against HCC. Whether a more potent anti-HBV agent with extremely low resistance profile, entecavir, is more beneficial to HBV-related cirrhotic patients is also unclear.
The Bureau of National Health Institute launched the reimbursement program for anti-HBV therapy since 2003 and extended this program to cirrhotic patients with HBV DNA level > 2000 IU/mL for long-term use since Aug, 2010. Taking this advantage, we may explore the above-mentioned clinical questions more easily.
To address these issues, we will first retrospectively collect a cohort of HBV-related cirrhosis patients. All the patients will be enrolled from the time before oral anti-HBV therapy is widely used. We will determine their baseline serum HBV-DNA levels using the stored sera and enrolled those with baseline HBV-DNA levels higher than 2000 IU/mL as our historical controls. Second, we will enroll a retrospective cohort of HBV-related cirrhotic patients from 2008 who had HBV-DNA levels higher than 2000 IU/mL and received indefinite therapy of entecavir. By comparing these two cohorts, we will be able to clarify whether indefinite viral suppression by entecavir is beneficial for the cirrhotic patients.
With comprehensive analysis, we wish to document that re-setting the risk level of HBV DNA from 140,000 IU/mL to 2,000 IU/mL is more beneficial for HBV-related cirrhotic patients and long-term entecavir does lower the risk of HCC further. These lines of evidence will assist in delivering appropriate and more aggressive treatment for these high-risk patients.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | liver cirrhosis group who received indefinite anti-viral treatment | |
| Historical control group | Liver cirrhotic patients who were enrolled before 2004 and did not receive treatment during the follow-up |
What is being measured
The primary outcome is the main question the study is designed to answer.
hepatocellular carcinoma
Measured: within a 10-year follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2013 (estimated)
- Study startOct 2011
- Primary completionJan 2012
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis B Virus-Related Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jia-Horng Kao, PhD, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01957618
- Sponsor's protocol ID
- 201110057RC
- Acronym
- CTEAM
- Status last verified
- Oct 2013
- First submitted
- 1 Oct 2013
- Last updated
- 8 Oct 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004 Oct 7;351(15):1521-31. doi: 10.1056/NEJMoa033364.
PubMed 15470215
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Follow-up Study of Chronic Hepatitis B Patients With Liver Cirrhosis Receiving Anti-HBV Therapy
- ClinicalTrials.gov ID
- NCT01957618
- Acronym / sponsor ID
- CTEAM / 201110057RC
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,500 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Jan 2012 (actual)
- Study completion
- Dec 2021 (estimated)
- First posted
- 8 Oct 2013 (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.
Hepatitis B virus (HBV) infection is a global health problem, especially in the endemic area like Taiwan, where there are more than 3 million chronic hepatitis B carriers. Patients with chronic HBV infection are at increased risk of developing cirrhosis, which may have disastrous complications, including hepatic decompensation, and hepatocellular carcinoma (HCC). The liver cirrhosis related complications accounts for the 8th leading cause of deaths in Taiwan; whereas, the HCC is the 2nd leading cause of deaths among all cancers. Therefore, it is prudent to develop strategies to prevent or halt the progression of liver cirrhosis.
For HBV patients who have already had cirrhosis, the main treatment objective is to reduce their risk of complications. A large-scale multicenter clinical trial showed that viral suppression using lamivudine in patients with advanced fibrosis effectively decreases the risk of HCC and liver-related complications. This study highlights the importance to treat HBV-related cirrhosis patients; however, several issues remain to be addressed.
The first issue is that this clinical trial only enrolled patients with positive HBeAg or HBV-DNA level >1.4 x105 IU/mL. However, the current recommended threshold for cirrhotic patients to start anti-viral treatment is 2000 IU/mL. Whether anti-HBV therapy benefits cirrhotic patients in this level is still unclear. Second, lamivudine was used in this clinical trial; however, the high resistant rate of lamivudine during treatment probably lowers its protective effect against HCC. Whether a more potent anti-HBV agent with extremely low resistance profile, entecavir, is more beneficial to HBV-related cirrhotic patients is also unclear.
The Bureau of National Health Institute launched the reimbursement program for anti-HBV therapy since 2003 and extended this program to cirrhotic patients with HBV DNA level > 2000 IU/mL for long-term use since Aug, 2010. Taking this advantage, we may explore the above-mentioned clinical questions more easily.
To address these issues, we will first retrospectively collect a cohort of HBV-related cirrhosis patients. All the patients will be enrolled from the time before oral anti-HBV therapy is widely used. We will determine their baseline serum HBV-DNA levels using the stored sera and enrolled those with baseline HBV-DNA levels higher than 2000 IU/mL as our historical controls. Second, we will enroll a retrospective cohort of HBV-related cirrhotic patients from 2008 who had HBV-DNA levels higher than 2000 IU/mL and received indefinite therapy of entecavir. By comparing these two cohorts, we will be able to clarify whether indefinite viral suppression by entecavir is beneficial for the cirrhotic patients.
With comprehensive analysis, we wish to document that re-setting the risk level of HBV DNA from 140,000 IU/mL to 2,000 IU/mL is more beneficial for HBV-related cirrhotic patients and long-term entecavir does lower the risk of HCC further. These lines of evidence will assist in delivering appropriate and more aggressive treatment for these high-risk patients.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment group | – | –liver cirrhosis group who received indefinite anti-viral treatment |
| Historical control group | – | –Liver cirrhotic patients who were enrolled before 2004 and did not receive treatment during the follow-up |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- from hospitals
Key inclusion criteria (10 listed)
- Age older than 20 years old.
- HBsAg (+) > 6 months
- Baseline serum HBV DNA ≧ 2000 IU/mL (10,000 copies/mL)
- Liver cirrhosis (Child A) before or at enrollment, diagnosed by 1). Liver biopsy（Metavir F4 or Ishak > F5） or 2). Ultrasonographic evidence of cirrhosis with signs of portal hypertension (splenomegaly or presence of esophageal or gastric varices)
- Receiving long-term anti-HBV therapy
Key exclusion criteria (6 listed)
- . Co-infection of HCV (anti-HCV (+)) or HIV
- . Alcoholism (alcohol consumption > 20 gm/day)
- . Serological evidence suggestive of autoimmune hepatitis, primary biliary cirrhosis, Wilson's disease and hemochromatosis
- . Liver decompensation (Child-Pugh classification of B or C)
- . Evidence of HCC at study entry
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
hepatocellular carcinoma
Time frame: within a 10-year follow-up.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2013.
- Background: PubMed 15470215Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004 Oct 7;351(15):1521-31. doi: 10.1056/NEJMoa033364.
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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.
Jia-Horng Kao, PhD principal investigator
National Taiwan University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatitis B Virus-Related Hepatocellular Carcinoma, run by National Taiwan University Hospital 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 10 inclusion and 6 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 8 Oct 2013. 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.
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?
hepatocellular carcinoma (time frame: within a 10-year follow-up.). 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 NCT01957618, which also lists 1 linked publication.
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 8 Oct 2013.