Chronic HBV With Severe ExacerbationPhase 3HBSAENCT01848743
Tenofovir Versus Lamivudine for Patients of Chronic Hepatitis B With Severe Acute Exacerbation
A Phase 3 study testing Tenofovir and lamivudine in people with Chronic HBV With Severe Exacerbation, run by Kaohsiung Veterans General Hospital. at 2 sites in Taiwan.
Trial summary
In Taiwan, 15% of general population had hepatitis B virus (HBV) infection, HBV is the leading cause of liver cirrhosis and hepatocellular carcinoma in Taiwan. After entering immune clearance, 10-30% of patients of chronic HBV develop acute exacerbation (AE) , some are mild but some developed hepatic decompensation or… Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Chronic HBV With Severe Exacerbation
- What is being tested?
- Tenofovir and lamivudine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 2 sitesTaiwan
- Study dates
- Apr 2013to Oct 2016
- Phase
- Phase 3
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HBsAg (+) > 6 months
- ALT > 5X ULN
- Prolongation of prothrombin time > 3 seconds and bilirubin level > 2 mg/dl
- 20-75 years old
Who cannot join
- HAV, HCV, HDV and HIV co-infection
- Concurrent hepatocellular carcinoma
- Drug, metabolic or alcohol as cause of hepatitis
- Anti-viral treatment in recent 6 mnths
- Pregnant woman
Trial locations and contacts
2 sites in 1 country.
Taiwan2 sites, 1 recruiting
- Recruiting
Kaohsiung Veterans General Hospigal
Kaohsiung, Taiwan, 813
Wei-Lun Tsai, MD, 886-7-3422121 ext. 2075, tsaiwl@yahoo.com.tw
Hi-Hung Chan, MD, PhD, 886-7-3422121 ext. 2074, hhchan@vghks.gov.tw
- Active, not recruiting
Kaohsiung Veterans General Hospital
Kaohsiung, Taiwan, 813
About this study
In Taiwan, 15% of general population had hepatitis B virus (HBV) infection, HBV is the leading cause of liver cirrhosis and hepatocellular carcinoma in Taiwan. After entering immune clearance, 10-30% of patients of chronic HBV develop acute exacerbation (AE) , some are mild but some developed hepatic decompensation or even death.
Previous study found that early use of lamivudine before bilirubin level is above 20 mg/dl can improve survival in chornic HBV with severe AE. From the study from Hongkong, lamivudine was found to have better survival than entecavir in chronic HBV with severe AE. Recent study from India found that tenofovir is able to improve survival in chronic HBV with severe AE. The aim of this study is to compare the effect of lamivudine and tenofovir for chronic HBV with severe AE.
The study aims to enroll 120 patients with chronic HBV defined as persistence of HBsAg for more than 6 months. Severe AE was defined as ALT > 400 U/L, prolongation of prothrombin time > 3 seconds, bilirubin > 2 mg/dl. Patients with hepatitis A, C, D or HIV infection, drug or alcoholic liver disease, hepatocellular carcinoma, under immuno-suppressive agents use, or previous use of anti-HBV agents are excluded. All enrolled patients are randomized into group A who received tenofovir 300 mg qd for 3 years and group B who received lamivuidne 100 mg qd for 6 months, followed by tenofovir 300mg qd for 30 months. Mortality rate and virological, biochemical and serological response were evaluated at 1,2,4,48,96 and 144 weeks. The values are expressed as mean + SD. Categorical variables were analyzed with Chi-square test or Fisher's exact test as appropriate and continuous variables were analyzed by Mann-Whitney test. Logistic regression test was applied to analyze the independent association of various variables with outcome. A p value < 0.05 was regarded as significant.
- Conditions
- Chronic HBV With Severe Exacerbation
- Being tested
- Tenofovir, lamivudine
- Keywords
- tenofovir, lamivudine, hepatitis B, acute exacerbation
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TenofovirDrug
Also called viread
lamivudineDrug
Also called zeffix
| Study group | Role | What they receive |
|---|---|---|
| Tenofovir | Active comparator | All enrolled patients are randomized to tenofovir arm who receives tenofovir 300 mg qd for 36 months Receives: Drug: Tenofovir |
| lamivudine | Placebo comparator | All enrolled patients are randomized to lamivudine arm who received lamivudine 100 mg qd for 6 months, followed by tenofovir for another 30 months. Receives: Drug: lamivudine |
What is being measured
The primary outcome is the main question the study is designed to answer.
6 months survival
6 months survival after treatment begins
Measured: 6 months after treatment begins
Secondary outcomes (3)
rapid virological response
Evaluate the relationship of rapid virological response ( at 1,2 and 4 weeks) and survival
Measured: 1,2 and 4 weeks after treatment
HBeAg seroconversion and virological response 1, 2, and 3 years after treatment
To evaluate the rate of HBeAg seroconversion and virological response 1, 2, and 3 years after treatment in the two arms
Measured: 1,2 and 3 years after treatment
Safety profile
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Measured: during and 6 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2013 (estimated)
- Study startApr 2013
- Primary completionApr 2016 (estimated)
- Study completionOct 2016 (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 Chronic HBV With Severe ExacerbationStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kaohsiung Veterans General Hospital.
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wei-Lun Tsai, Kaohsiung Veterans General Hospital.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01848743
- Sponsor's protocol ID
- Gilead IN-US-174- 0190
- Acronym
- HBSAE
- Status last verified
- Sep 2014
- First submitted
- 24 Apr 2013
- Last updated
- 16 Sep 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lu CM, Cheng JS, Sun WC, Chen WC, Tsay FW, Wang HM, Tsai TJ, Kao SS, Li YD, Li YR, Lin HS, Yin CH, Tsai WL. Randomized Controlled Study of Tenofovir versus Lamivudine Followed by Tenofovir in Severe Exacerbation of Hepatitis B. Antimicrob Agents Chemother. 2022 Feb 15;66(2):e0166421. doi: 10.1128/AAC.01664-21. Epub 2021 Nov 22.
PubMed 34807763
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tenofovir Versus Lamivudine for Patients of Chronic Hepatitis B With Severe Acute Exacerbation
- ClinicalTrials.gov ID
- NCT01848743
- Acronym / sponsor ID
- HBSAE / Gilead IN-US-174- 0190
- Conditions
- Chronic HBV With Severe Exacerbation
- Keywords
- tenofovir, lamivudine, hepatitis B, acute exacerbation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Kaohsiung Veterans General Hospital.University, hospital or other
- Study start
- Apr 2013
- Primary completion
- Apr 2016 (estimated)
- Study completion
- Oct 2016 (estimated)
- First posted
- 7 May 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.
In Taiwan, 15% of general population had hepatitis B virus (HBV) infection, HBV is the leading cause of liver cirrhosis and hepatocellular carcinoma in Taiwan. After entering immune clearance, 10-30% of patients of chronic HBV develop acute exacerbation (AE) , some are mild but some developed hepatic decompensation or even death.
Previous study found that early use of lamivudine before bilirubin level is above 20 mg/dl can improve survival in chornic HBV with severe AE. From the study from Hongkong, lamivudine was found to have better survival than entecavir in chronic HBV with severe AE. Recent study from India found that tenofovir is able to improve survival in chronic HBV with severe AE. The aim of this study is to compare the effect of lamivudine and tenofovir for chronic HBV with severe AE.
The study aims to enroll 120 patients with chronic HBV defined as persistence of HBsAg for more than 6 months. Severe AE was defined as ALT > 400 U/L, prolongation of prothrombin time > 3 seconds, bilirubin > 2 mg/dl. Patients with hepatitis A, C, D or HIV infection, drug or alcoholic liver disease, hepatocellular carcinoma, under immuno-suppressive agents use, or previous use of anti-HBV agents are excluded. All enrolled patients are randomized into group A who received tenofovir 300 mg qd for 3 years and group B who received lamivuidne 100 mg qd for 6 months, followed by tenofovir 300mg qd for 30 months. Mortality rate and virological, biochemical and serological response were evaluated at 1,2,4,48,96 and 144 weeks. The values are expressed as mean + SD. Categorical variables were analyzed with Chi-square test or Fisher's exact test as appropriate and continuous variables were analyzed by Mann-Whitney test. Logistic regression test was applied to analyze the independent association of various variables with outcome. A p value < 0.05 was regarded as significant.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tenofovir | Active comparator | Drug: TenofovirAll enrolled patients are randomized to tenofovir arm who receives tenofovir 300 mg qd for 36 months |
| lamivudine | Placebo comparator | Drug: lamivudineAll enrolled patients are randomized to lamivudine arm who received lamivudine 100 mg qd for 6 months, followed by tenofovir for another 30 months. |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- HBsAg (+) > 6 months
- ALT > 5X ULN
- Prolongation of prothrombin time > 3 seconds and bilirubin level > 2 mg/dl
- 20-75 years old
Key exclusion criteria (5 listed)
- HAV, HCV, HDV and HIV co-infection
- Concurrent hepatocellular carcinoma
- Drug, metabolic or alcohol as cause of hepatitis
- Anti-viral treatment in recent 6 mnths
- Pregnant woman
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 |
|---|---|---|
| TenofovirAlso: viread | Drug | Tenofovir |
| lamivudineAlso: zeffix | Drug | lamivudine |
Primary outcome
6 months survival
Time frame: 6 months after treatment begins
6 months survival after treatment begins
3 secondary outcomes
rapid virological response
Time frame: 1,2 and 4 weeks after treatment
HBeAg seroconversion and virological response 1, 2, and 3 years after treatment
Time frame: 1,2 and 3 years after treatment
Safety profile
Time frame: during and 6 months after treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2014.
- Derived from this study: PubMed 34807763Lu CM, Cheng JS, Sun WC, Chen WC, Tsay FW, Wang HM, Tsai TJ, Kao SS, Li YD, Li YR, Lin HS, Yin CH, Tsai WL. Randomized Controlled Study of Tenofovir versus Lamivudine Followed by Tenofovir in Severe Exacerbation of Hepatitis B. Antimicrob Agents Chemother. 2022 Feb 15;66(2):e0166421. doi: 10.1128/AAC.01664-21. Epub 2021 Nov 22.
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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tenofovir and lamivudine in people with Chronic HBV With Severe Exacerbation, run by Kaohsiung Veterans General Hospital. at 2 sites 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 4 inclusion and 5 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 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Wei-Lun Tsai, M.D. (886-7-3422121 ext. 2075, tsaiwl@yahoo.com.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6 months survival (time frame: 6 months after treatment begins). 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 NCT01848743, 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 16 Sep 2014.