Hepatitis B, ChronicPhase 4ATTACHNCT04780204
Effectiveness of Antiviral Treatment in Cirrhotic Patients With Low-level Hepatitis B Virus DNA Levels
A Phase 4 study testing Treatment in people with Hepatitis B, Chronic, run by Asan Medical Center at 10 sites in South Korea.
Trial summary
Multicenter, Open-label, Single arm Trial with Matched Historical controls. Male and female adults with compensated liver cirrhosis due to chronic hepatitis B virus infection who have low-level viremia. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- Treatment
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 600 participants
- Where
- 10 sitesSouth Korea
- Study dates
- 23 Aug 2021to Dec 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent prior to study entry
- Age ≥30 years and ≤80 years at the time of screening
- Chronic hepatitis B infection defined as HBsAg (+) or HBV DNA (+) for at least 6 months prior to the Screening visit, or medical records indication a chronic hepatitis B virus infection by meeting all of the following criteria at the time of screening. (1) HBsAg (+), (2) HBV DNA (+), and (3) HBcAb IgM (-)
- Either HBeAg (+) or HBeAg (-)
- Serum HBV DNA levels ≥20 IU/mL and <2,000 IU/mL at the time of screening
- Evidence of liver cirrhosis defined as meeting any of the following criteria:
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- Radiological evidence of liver cirrhosis by ultrasound, CT, or MRI
- Platelet count <150,000 /mm3
- Presence of esophageal or gastric varices by endoscopy in 2 years before the timing of screening
- Clinically significant portal hypertension
- Fibroscan ≥12.0 kPa (if the test was done in 6 months before the time of screening)
- Estimated creatinine clearance ≥30 ml/min (by calculation of creatinine clearance or using the CKD-EPI equation)
- Ability to comply with all study requirements
Who cannot join
- Confirmed known co-infection with HCV, HIV, or HDV
- Current alcohol (60g/day) or substance abuse judged by the investigator that will potentially interfere with subject compliance
- Any history of, or current evidence of, clinical hepatic decompensation (e.g., ascites, encephalopathy, variceal hemorrhage, or Child-Pugh score of ≥8, with the exception of Gilbert syndrome) in 1 year before the time of screening
- Currently on or have received therapy with Interferon or immunosuppressant (including systemic chemotherapy) within 12 months prior to the screening
- Requirement for chronic use of systemic immunosuppressant including, but not limited to, corticosteroid (prednisone equivalent of >40 mg/day for >2 weeks), azathioprine, or monoclonal antibodies
- Received solid organ or bone marrow transplant
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- History of severe, life-threatening or other significant sensitivity to any excipients of the study drugs
- Any other clinical conditions (cardiovascular, respiratory, neurologic, or renal conditions) or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements.
- Currently on or have received antiviral treatment for ≥ 2 weeks within 6 months prior to the screening
- History or current evidence of hepatocellular carcinoma (HCC), or high α-fetoprotein (AFP) > 20 ng/mL. But, the patients with AFP > 20 ng/mL can be enrolled if AFP shows decreasing trend and there is no evidence of HCC by dynamic CT or MRI)
- Malignancy other than hepatocellular carcinoma within the 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (within 2 years prior to screening with confirmation of no evidence of disease). Subjects under evaluation for possible malignancy are not eligible.
- Concurrent enrollment in another clinical study for other type of antiviral treatment for CHB or immune modulatory drug within 3 months prior to randomization, participation to an observational (non-interventional) clinical studies or interventional studies not using anti-HBV or immune modulatory drugs, or during the follow-up period of an interventional study are not exclusion criteria.
- Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
South Korea10 sites
Kyungpook National University Hospital
Daegu
Asan Medical Center
Seoul
Chung-Ang University Hospital
Seoul
Konkuk University Hospital
Seoul
Korea University Guro Hospital
Seoul
Kyung-Hee University Hospital
Seoul
Samsung Medical center
Seoul
Seoul National University Bundang Hospital
Seoul
Seoul National University Hospital
Seoul
Ulsan University Hospital
Ulsan
About this study
Official title: A Multicenter, Open-label, Single Arm Trial for the Effectiveness of Antiviral Treatment in Cirrhotic Patients With Low-level Hepatitis B Virus DNA Levels With a Comparison to Matched Historical Controls (ATTACH)
Multicenter, Open-label, Single arm Trial with Matched Historical controls. Male and female adults with compensated liver cirrhosis due to chronic hepatitis B virus infection who have low-level viremia.
To assess the efficacy of Tenofovir Alafenamide (TAF) in reducing liver-related events (hepatocellular carcinoma, liver-related events and death, decompensated liver cirrhosis) in cirrhotic chronic hepatitis B patients with low-level viremia compared with matched historical controls.
Read the detailed description
- This clinical trial is a multicenter, open label, single arm study in cirrhotic chronic hepatitis B patients with low-level viremia.
- Approximately 200 subjects meeting eligibility criteria will be enrolled and randomized (1:2) to Treatment Arm (A) or , Matched Historical Controls Arm (B), as below:
- Treatment Arm (A): 200 subjects, TAF 25mg once daily with food for 3 years
- Matched Historical Controls Arm (B): 400 subjects, patients who did not receive antiviral treatment during their follow-up period, and matched with the treatment group in a 1:1 ratio according to their baseline characteristics
- Treatment Arm is scheduled to be followed up to 3 years.
The analysis population of this study consists of the Full Analysis Set (FAS), which can evaluate efficacy. The treatment group includes patients who received any dose of study medication (TAF), while the control group consists of patients who did not receive antiviral treatment and were matched by propensity score (PS) from those under observation. Unless otherwise specified, the FAS will be used for primary and secondary efficacy endpoints.
Statistical analyses for the primary efficacy endpoint will be performed at a two-sided significance level of 5%, aligned with the sample size calculation.
PS will be estimated using logistic regression, incorporating variables such as age, gender, HBeAg positivity, HBV DNA level, ALT, platelet count, albumin, total bilirubin, creatinine, prothrombin time, diabetes, hypertension, and family history of hepatocellular carcinoma. The groups will be matched 1:2 using nearest neighbor matching. Baseline characteristics between the matched groups will be compared using standardized mean difference (SMD), with an absolute SMD <0.1 indicating good balance.
The 3-year cumulative incidence of the primary endpoint will be estimated using the Kaplan-Meier method. For comparisons between PS-matched groups, a Cox proportional hazards model with robust variance estimation will be used to account for matching, reporting HR and 95% confidence intervals.
For hepatocellular carcinoma incidence, mortality, liver transplantation, decompensated liver function (Child-Pugh score ≥8), and cirrhosis-related complications, 1-, 2-, and 3-year incidence rates will be estimated with Kaplan-Meier. Cox models with robust variance will be used for group comparisons, reporting HR and 95% confidence intervals.
HBsAg loss and viral response (HBV DNA <15 IU/mL) are binary outcomes, summarized by frequency and proportion in each group. Comparisons will be made using a Poisson regression model with Generalized Estimating Equations (GEE), reporting relative risk (RR) and 95% confidence intervals.
Fibroscan changes, treatment response, duration, and health-related quality of life by disease status (hepatitis, cirrhosis, hepatocellular carcinoma) will be analyzed using GEE, accounting for the matched-pair design.
In the PS-matched retrospective control group, the 1-, 2-, and 3-year cumulative probabilities of initiating antiviral therapy due to serum HBV DNA ≥2,000 IU/mL will be estimated via Kaplan-Meier.
Two official analyses will be conducted: an interim analysis (using data collected by October 2024) and a final analysis. No correction for type 1 error inflation from multiple testing will be applied in the interim analysis.
For sensitivity analysis, multivariable analyses will be performed using the unmatched dataset for primary and secondary endpoints. Depending on outcome type, Cox models and Poisson regression will be employed, using the covariates from the PS estimation for adjustment.
- Conditions
- Hepatitis B, Chronic
- Being tested
- Treatment
- 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.
TreatmentDrug
Also called Tenofovir alafenamide
Tenofovir Alafenamide 25 mg oral once daily
| Study group | Role | What they receive |
|---|---|---|
| Antiviral Treatment | Experimental | Tenofovir Alafenamide 25mg once daily , Oral Receives: Drug: Treatment |
| Matched Historical Controls | No intervention | Patients who did not receive antiviral treatment during their follow-up period, and matched with the treatment group in a 1:2 ratio according to their baseline characteristics |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative incidence rate of composite clinical events
hepatocellular carcinoma, death, liver transplantation, decompensated liver cirrhosis defined as Child-Pugh score ≥8, liver cirrhosis-related complications,liver-related unexpected hospital admission
Measured: From randomization the composite clinical events will be collected every 6weeks , assessed up to 36months
Secondary outcomes (1)
Cumulative incidence
Death, hepatocellular carcinoma , Liver transplantation, decompensated liver cirrhosis, liver cirrhosis-related complications, subjects with HBsAg seroclearance, subjects with HBV DNA <15 IU/mL, Serial changes of liver stiffness assessed by Fibroscan
Measured: From randomization the composite clinical events will be collected every 1year , assessed up to 3years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2021
- Study start23 Aug 2021
- Primary completionJan 2027 (estimated)
- Study completionDec 2027 (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 Asan Medical CenterThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Asan Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Evidence-Based Healthcare Collaborating Agency
- Responsible party
- Principal investigator, Young-Suk Lim, Asan Medical Center
- Investigators
- Young-Suk Lim, PhD, Principal investigator, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04780204
- Sponsor's protocol ID
- IN-KR-320-6132
- Acronym
- ATTACH
- Status last verified
- Nov 2026
- First submitted
- 1 Mar 2021
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label, Single Arm Trial for the Effectiveness of Antiviral Treatment in Cirrhotic Patients With Low-level Hepatitis B Virus DNA Levels With a Comparison to Matched Historical Controls (ATTACH)
- ClinicalTrials.gov ID
- NCT04780204
- Acronym / sponsor ID
- ATTACH / IN-KR-320-6132
- Conditions
- Hepatitis B, Chronic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Collaborators
- National Evidence-Based Healthcare Collaborating Agency
- Study start
- 23 Aug 2021 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 3 Mar 2021 (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.
Multicenter, Open-label, Single arm Trial with Matched Historical controls. Male and female adults with compensated liver cirrhosis due to chronic hepatitis B virus infection who have low-level viremia.
To assess the efficacy of Tenofovir Alafenamide (TAF) in reducing liver-related events (hepatocellular carcinoma, liver-related events and death, decompensated liver cirrhosis) in cirrhotic chronic hepatitis B patients with low-level viremia compared with matched historical controls.
Detailed description
- This clinical trial is a multicenter, open label, single arm study in cirrhotic chronic hepatitis B patients with low-level viremia.
- Approximately 200 subjects meeting eligibility criteria will be enrolled and randomized (1:2) to Treatment Arm (A) or , Matched Historical Controls Arm (B), as below:
- Treatment Arm (A): 200 subjects, TAF 25mg once daily with food for 3 years
- Matched Historical Controls Arm (B): 400 subjects, patients who did not receive antiviral treatment during their follow-up period, and matched with the treatment group in a 1:1 ratio according to their baseline characteristics
- Treatment Arm is scheduled to be followed up to 3 years.
The analysis population of this study consists of the Full Analysis Set (FAS), which can evaluate efficacy. The treatment group includes patients who received any dose of study medication (TAF), while the control group consists of patients who did not receive antiviral treatment and were matched by propensity score (PS) from those under observation. Unless otherwise specified, the FAS will be used for primary and secondary efficacy endpoints.
Statistical analyses for the primary efficacy endpoint will be performed at a two-sided significance level of 5%, aligned with the sample size calculation.
PS will be estimated using logistic regression, incorporating variables such as age, gender, HBeAg positivity, HBV DNA level, ALT, platelet count, albumin, total bilirubin, creatinine, prothrombin time, diabetes, hypertension, and family history of hepatocellular carcinoma. The groups will be matched 1:2 using nearest neighbor matching. Baseline characteristics between the matched groups will be compared using standardized mean difference (SMD), with an absolute SMD <0.1 indicating good balance.
The 3-year cumulative incidence of the primary endpoint will be estimated using the Kaplan-Meier method. For comparisons between PS-matched groups, a Cox proportional hazards model with robust variance estimation will be used to account for matching, reporting HR and 95% confidence intervals.
For hepatocellular carcinoma incidence, mortality, liver transplantation, decompensated liver function (Child-Pugh score ≥8), and cirrhosis-related complications, 1-, 2-, and 3-year incidence rates will be estimated with Kaplan-Meier. Cox models with robust variance will be used for group comparisons, reporting HR and 95% confidence intervals.
HBsAg loss and viral response (HBV DNA <15 IU/mL) are binary outcomes, summarized by frequency and proportion in each group. Comparisons will be made using a Poisson regression model with Generalized Estimating Equations (GEE), reporting relative risk (RR) and 95% confidence intervals.
Fibroscan changes, treatment response, duration, and health-related quality of life by disease status (hepatitis, cirrhosis, hepatocellular carcinoma) will be analyzed using GEE, accounting for the matched-pair design.
In the PS-matched retrospective control group, the 1-, 2-, and 3-year cumulative probabilities of initiating antiviral therapy due to serum HBV DNA ≥2,000 IU/mL will be estimated via Kaplan-Meier.
Two official analyses will be conducted: an interim analysis (using data collected by October 2024) and a final analysis. No correction for type 1 error inflation from multiple testing will be applied in the interim analysis.
For sensitivity analysis, multivariable analyses will be performed using the unmatched dataset for primary and secondary endpoints. Depending on outcome type, Cox models and Poisson regression will be employed, using the covariates from the PS estimation for adjustment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Antiviral Treatment | Experimental | Drug: TreatmentTenofovir Alafenamide 25mg once daily , Oral |
| Matched Historical Controls | No intervention | –Patients who did not receive antiviral treatment during their follow-up period, and matched with the treatment group in a 1:2 ratio according to their baseline characteristics |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Willing and able to provide written informed consent prior to study entry
- Age ≥30 years and ≤80 years at the time of screening
- Chronic hepatitis B infection defined as HBsAg (+) or HBV DNA (+) for at least 6 months prior to the Screening visit, or medical records indication a chronic hepatitis B virus infection by meeting all of the following criteria at the time of screening. (1) HBsAg (+), (2) HBV DNA (+), and (3) HBcAb IgM (-)
- Either HBeAg (+) or HBeAg (-)
- Serum HBV DNA levels ≥20 IU/mL and <2,000 IU/mL at the time of screening
Key exclusion criteria (13 listed)
- Confirmed known co-infection with HCV, HIV, or HDV
- Current alcohol (60g/day) or substance abuse judged by the investigator that will potentially interfere with subject compliance
- Any history of, or current evidence of, clinical hepatic decompensation (e.g., ascites, encephalopathy, variceal hemorrhage, or Child-Pugh score of ≥8, with the exception of Gilbert syndrome) in 1 year before the time of screening
- Currently on or have received therapy with Interferon or immunosuppressant (including systemic chemotherapy) within 12 months prior to the screening
- Requirement for chronic use of systemic immunosuppressant including, but not limited to, corticosteroid (prednisone equivalent of >40 mg/day for >2 weeks), azathioprine, or monoclonal antibodies
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 |
|---|---|---|
| TreatmentAlso: Tenofovir alafenamideTenofovir Alafenamide 25 mg oral once daily | Drug | Antiviral Treatment |
Primary outcome
Cumulative incidence rate of composite clinical events
Time frame: From randomization the composite clinical events will be collected every 6weeks , assessed up to 36months
hepatocellular carcinoma, death, liver transplantation, decompensated liver cirrhosis defined as Child-Pugh score ≥8, liver cirrhosis-related complications,liver-related unexpected hospital admission
1 secondary outcome
Cumulative incidence
Time frame: From randomization the composite clinical events will be collected every 1year , assessed up to 3years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
- 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.
Young-Suk Lim, PhD principal investigator
Asan Medical Center
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Treatment in people with Hepatitis B, Chronic, run by Asan Medical Center at 10 sites 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 13 inclusion and 13 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: under way, not looking for participants, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites 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?
This study is still under way. Results are not available in the source record yet.
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?
Cumulative incidence rate of composite clinical events (time frame: From randomization the composite clinical events will be collected every 6weeks , assessed up to 36months). 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 4 Nov 2026.