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Chronic Hepatitis bPhase 4ATTENTIONNCT03753074

Effectiveness of TAF in Reducing Clinical Events in CHB Patients Beyond Treatment Indications by Current Guidelines

A Phase 4 study testing Tenofovir Alafenamide in people with Chronic Hepatitis b, run by Young-Suk Lim at 10 sites in South Korea.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Treatment with Tenofovir Alafenamide(TAF) in Chronic Hepatitis B (CHB) patients classified as beyond treatment indication of current international guidelines (e.g. aged more than 40 years old and 4 ≤ log HBV-DNA IU/mL < 8) is expected to bring improvement in long-term clinical outcomes. Read more about this study

Who is it for?
Ages 40 to 80 years
Conditions the study is for
Chronic Hepatitis b
What is being tested?
Tenofovir Alafenamide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
780 participants
Where
10 sitesSouth Korea
Study dates
18 Feb 2019to 31 Dec 2031
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 40 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Inclusion Criteria: Patients must meet all of the following criteria to be eligible to participate in the study

  1. Patient must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
  2. Male or female, 40 to 80 years of age
  3. Positive for HBsAg or HBV DNA for at least 6 months or more
  4. HBeAg positive or negative
  5. No evidence of liver cirrhosis (platelet count ≥100,000/mm3)
  6. serum HBV DNA ≥ 4 log10 IU/mL and ≤ 8 log10 IU/mL
  7. Serum ALT level <70 if male, <50 if female
  8. Estimated creatinine clearance ≥ 30 ml/min based on serum creatinine as measured at the screening evaluation
  9. Patient is willing and able to comply with all study requirements

Exclusion Criteria: Patients who meet any of the following exclusion criteria are not to be enrolled in this study

  1. Co-infection with HCV, HDV, HIV (Confirmed by nucleic acid tests)
  2. Abusing alcohol (more than 60 g/day) or illicit drugs
  3. Patients with history of hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage)

4-1) Evidence of cirrhosis, including any of follows:

  1. Platelet count <100,000/mm3
  2. Esophagogastric varices on endoscopy
  3. Evidence of clinically significant portal hypertension
  4. Fibroscan ≥ 12.0 kPa (If the test was done in 3 months before the time of screening.) and confirmed to have liver cirrhosis by an investigator

4-2) 40≤ALT levels<70 IU/L (males) or 40≤ ALT levels<50 IU/L (females) with evidence of significant fibrosis(F2; ≥7.2 kPa) as measured by either liver biopsy, Fibroscan or MR elastograpy performed within 3 months.

  1. Received interferon or other immunomodulatory treatment for HBV infection in the 12 months before screening for this study
  2. Medical condition that requires concurrent use of systemic corticosteroid or other immunosuppressive agents
  3. Received solid organ or bone marrow transplant
  4. Known hypersensitivity to study drugs, metabolites, or formulation excipients
  5. Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the patient unsuitable for the study or unable to comply with dosing requirements
  6. Use of investigational agents within 6 months of screening, unless allowed by the Sponsor or Investigator
  7. Significant renal, cardiovascular, pulmonary, or neurological disease in the opinion of the Investigator
  8. Any malignant tumor in the preceding five years. However, a history of treated malignancy (other than HCC) is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding three years
  9. Pregnant or breastfeeding or willing to be pregnant
  10. Participating in other clinical trials to administer medication. However, it is possible to participate if it is not an antiviral agent or immunosuppressant related clinical trial.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

South Korea10 sites

  • Kyungpook National University Hospital

    Daegu

  • Seoul National University Bundang Hospital

    Seongnam

  • Asan Medical Center

    Seoul, 05505

  • 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 Hospital

    Seoul

  • Ulsan University Hospital

    Ulsan

Other trials in South Korea

About this study

Official title: A Multinational, Multicenter, Open-label, Randomized Controlled Trial to Investigate the Effectiveness of Tenofovir Alafenamide in Reducing Clinical Events in Chronic Hepatitis B Patients Beyond Treatment Indications by Current Guidelines

Treatment with Tenofovir Alafenamide(TAF) in Chronic Hepatitis B (CHB) patients classified as beyond treatment indication of current international guidelines (e.g. aged more than 40 years old and 4 ≤ log HBV-DNA IU/mL < 8) is expected to bring improvement in long-term clinical outcomes. This expected result may expand the treatment indications in patients with CHB based on age and HBV-DNA in contrast to current international guidelines of CHB.

Read the detailed description

Study objectives: To investigate whether TAF treatment reduce clinical events (HCC, death, liver decompensation, portal hypertensive complications, and liver transplantation) in CHB patients beyond treatment indications by current guidelines

Study procedure: 780 subjects will be randomized in a 1:1 ratio (A:B) either to receive TAF 25 mg QD or to receive best supportive care after stratification according to the HBeAg status.

The study duration is 12 years. During treatment period, among treatment arm B, subjects who are indicated for antiviral treatment will be treated with TAF as follows:

  1. Based on the AASLD 2018 Guidelines of CHB (ALT 70≥ for male, 50≥ for female)
  2. 40≤ALT levels<70 IU/L (males) or 40≤ ALT levels<50 IU/L (females) with evidence of significant fibrosis(F2; ≥7.2 kPa) as measured by either liver biopsy, Fibroscan or MR elastograpy performed within 3 months.
  3. If they were clinically judged to have cirrhosis by investigators and confirmed with Fibroscan (≥ 12.0 kPa).
  • Treatment Arm A: 390 subjects administered TAF 25 mg once daily
  • Treatment Arm B: 390 subjects received best supportive care

The primary analysis will occur at Year 4 with the primary endpoint being occurrence of composite events during follow-up observation

Being tested
Tenofovir Alafenamide
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 AlafenamideDrug

    Also called Vemlidy

    Tenofovir Alafenamide 25mg, Tablet, Oral, Daily

Study groups in NCT03753074
Study groupRoleWhat they receive
Treatment Arm A (TAF)Experimental390 subjects administered Tenofovir Alafenamide 25 mg once daily
Receives: Drug: Tenofovir Alafenamide
Treatment Arm B (Best supportive care)No intervention390 subjects received best supportive care During treatment period, among treatment arm B, subjects who are indicated for antiviral treatment will be treated with TAF as follows: 1. Based on the AASLD 2018 Guidelines of CHB (ALT 70≥ for male, 50≥ for female) 2. 40≤ALT levels<70 IU/L (males) or 40≤ ALT levels<50 IU/L (females) with evidence of significant fibrosis(F2; ≥7.2 kPa) as measured by either liver biopsy, Fibroscan or MR elastograpy performed within 3 months. 3. If they were clinically judged to have cirrhosis by investigators and confirmed with Fibroscan (≥ 12.0 kPa).

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. the occurrence of composite events during follow-up observation

    the occurrence of composite events during follow-up observation(including death, liver transplantation, or decompensated liver diseases [Child-Pugh score≥7], complications of portal hypertension [ascites, gastroesophageal varices] or HCC

    Measured: At year 4

Secondary outcomes (27)

  1. Cumulative rate of patients with clinical events

    Cumulative rate of patients with clinical events (death, liver transplantation, liver decompensation, portal hypertensive complications, and HCC)

    Measured: At year 4, 8 and 12

  2. Cumulative incidence rate of HCC

    Cumulative incidence rate of HCC

    Measured: At year 4, 8 and 12

  3. All-cause mortality

    All-cause mortality

    Measured: At year 4, 8 and 12

  4. Cumulative incidence rate of liver transplantation

    Cumulative incidence rate of liver transplantation

    Measured: At year 4, 8 and 12

  5. Cumulative incidence rate of liver decompensation

    Cumulative incidence rate of liver decompensation

    Measured: At year 4, 8 and 12

  6. Cumulative incidence rate of portal hypertensive complications

    Cumulative incidence rate of portal hypertensive complications

    Measured: At year 4, 8 and 12

  7. Rate of receiving nucleos(t)ide analogue by meeting reimbursement criteria of treatment among Treatment ARM B subjects

    Rate of receiving nucleos(t)ide analogue by meeting reimbursement criteria of treatment among Treatment ARM B subjects

    Measured: At year 4, 8 and 12

  8. Virologic response defined as HBV DNA less than 15 IU/mL

    Virologic response defined as HBV DNA less than 15 IU/mL

    Measured: At year 4, 8 and 12

  9. Rate of ALT normalization

    Rate of ALT normalization if baseline ALT is elevated

    Measured: At year 4, 8 and 12

  10. Rate of HBeAg seroclearance and seroconversion

    Rate of HBeAg seroclearance and seroconversion among HBeAg-positive patients

    Measured: At year 4, 8 and 12

  11. Change of fibroscan

    Change of fibroscan

    Measured: At year 4, 8 and 12

  12. Change of APRI index

    Change of APRI index

    Measured: At year 4, 8 and 12

  13. Change of FIB-4

    Change of FIB-4

    Measured: At year 4, 8 and 12

  14. Cumulative incidence rate of HCC among HBeAg-positive or HBeAg-negative Patients

    Cumulative incidence rate of HCC among HBeAg-positive or HBeAg-negative Patients

    Measured: At year 4, 8 and 12

  15. All cause-mortality among HBeAg-positive or HBeAg-negative

    All cause-mortality among HBeAg-positive or HBeAg-negative

    Measured: At year 4, 8 and 12

  16. Cumulative incidence rate of liver transplantation among HBeAg-positive or HBeAg-negative

    Cumulative incidence rate of liver transplantation among HBeAg-positive or HBeAg-negative

    Measured: At year 4, 8 and 12

  17. Cumulative incidence rate of liver decompensation among HBeAg-positive or HBeAg-negative

    Cumulative incidence rate of liver decompensation among HBeAg-positive or HBeAg-negative

    Measured: At year 4, 8 and 12

  18. Cumulative incidence rate of portal hypertensive complications among HBeAg-positive or HBeAg-negative

    Cumulative incidence rate of portal hypertensive complications amongHBeAg-positive or HBeAg-negative

    Measured: At year 4, 8 and 12

  19. Cumulative incidence rate of HCC among subjects according to baseline ALT level (normal ALT and elevated ALT)

    Cumulative incidence rate of HCC amongsubjects according to baseline ALT level (normal ALT and elevated ALT)

    Measured: At year 4, 8 and 12

  20. All cause-mortality among subjects according to baseline ALT level (normal ALT and elevated ALT)

    All cause-mortality among subjects according to baseline ALT level (normal ALT and elevated ALT)

    Measured: At year 4, 8 and 12

  21. Cumulative incidence rate of liver transplantation among subjects according to baseline ALT level (normal ALT and elevated ALT)

    Cumulative incidence rate of liver transplantation among subjects according to baseline ALT level (normal ALT and elevated ALT)

    Measured: At year 4, 8 and 12

  22. Cumulative incidence rate of liver decompensation among subjects according to baseline ALT level (normal ALT and elevated ALT)

    Cumulative incidence rate of liver decompensation among subjects according to baseline ALT level (normal ALT and elevated ALT)

    Measured: At year 4, 8 and 12

  23. Cumulative incidence rate of portal hypertensive complications among subjects according to baseline ALT level (normal ALT and elevated ALT)

    Cumulative incidence rate of portal hypertensive complications among subjects according to baseline ALT level (normal ALT and elevated ALT)

    Measured: At year 4, 8 and 12

  24. Cumulative and annual rate of patients with clinical events (death, liver transplantation, liver decompensation, portal hypertensive complications, and HCC) after excluding patients who occurrs clinical events within 6 months of enrollment

    Cumulative and annual rate of patients with clinical events (death, liver transplantation, liver decompensation, portal hypertensive complications, and HCC) after excluding patients who occurrs clinical events within 6 months of enrollment

    Measured: At year 4, 8 and 12

  25. Cumulative and annual rate of patients with clinical events (death, liver transplantation, liver decompensation, portal hypertensive complications, and HCC) after excluding patients who occurrs clinical events within 12 months of enrollment

    Cumulative and annual rate of patients with clinical events (death, liver transplantation, liver decompensation, portal hypertensive complications, and HCC) after excluding patients who occurrs clinical events within 12 months of enrollment

    Measured: At year 4, 8 and 12

  26. Cumulative and annual rate of patients with clinical events in patients with normal ALT (<40 U/L) at the time of enrollment, after excluding patients who occurrs clinical

    Cumulative and annual rate of patients with clinical events (death, liver transplantation, liver decompensation, portal hypertensive complications, and HCC) in patients with normal ALT (<40 U/L) at the time of enrollment, after excluding patients who occurrs clinical events within 6 months of enrollment

    Measured: At year 4, 8 and 12

  27. Cumulative and annual rate of patients with clinical events in patients with normal ALT (<40 U/L) at the time of enrollment, after excluding patients who occurrs clinical events within 12 months of enrollment

    Cumulative and annual rate of patients with clinical events (death, liver transplantation, liver decompensation, portal hypertensive complications, and HCC) in patients with normal ALT (<40 U/L) at the time of enrollment, after excluding patients who occurrs clinical events within 12 months of enrollment

    Measured: At year 4, 8 and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Nov 2018
  2. Study start18 Feb 2019
  3. Primary completion31 Dec 2031 (estimated)
  4. Study completion31 Dec 2031 (estimated)

Resources

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
780 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03753074
Sponsor's protocol ID
IN-KR-320-5358
Acronym
ATTENTION
Status last verified
Nov 2026
First submitted
22 Nov 2018
Last updated
4 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. No abstract available.

    PubMed 29405329

  • European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18.

    PubMed 28427875

  • Tseng TC, Kao JH. Treating Immune-tolerant Hepatitis B. J Viral Hepat. 2015 Feb;22(2):77-84. doi: 10.1111/jvh.12370. Epub 2014 Nov 25.

    PubMed 25424771

  • Andreani T, Serfaty L, Mohand D, Dernaika S, Wendum D, Chazouilleres O, Poupon R. Chronic hepatitis B virus carriers in the immunotolerant phase of infection: histologic findings and outcome. Clin Gastroenterol Hepatol. 2007 May;5(5):636-41. doi: 10.1016/j.cgh.2007.01.005. Epub 2007 Apr 11.

    PubMed 17428739

  • Hui CK, Leung N, Yuen ST, Zhang HY, Leung KW, Lu L, Cheung SK, Wong WM, Lau GK; Hong Kong Liver Fibrosis Study Group. Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase. Hepatology. 2007 Aug;46(2):395-401. doi: 10.1002/hep.21724.

    PubMed 17628874

  • Kennedy PTF, Sandalova E, Jo J, Gill U, Ushiro-Lumb I, Tan AT, Naik S, Foster GR, Bertoletti A. Preserved T-cell function in children and young adults with immune-tolerant chronic hepatitis B. Gastroenterology. 2012 Sep;143(3):637-645. doi: 10.1053/j.gastro.2012.06.009. Epub 2012 Jun 15.

    PubMed 22710188

  • Lai M, Hyatt BJ, Nasser I, Curry M, Afdhal NH. The clinical significance of persistently normal ALT in chronic hepatitis B infection. J Hepatol. 2007 Dec;47(6):760-7. doi: 10.1016/j.jhep.2007.07.022. Epub 2007 Sep 24.

    PubMed 17928090

  • Kumar M, Sarin SK, Hissar S, Pande C, Sakhuja P, Sharma BC, Chauhan R, Bose S. Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT. Gastroenterology. 2008 May;134(5):1376-84. doi: 10.1053/j.gastro.2008.02.075. Epub 2008 Feb 29.

    PubMed 18471514

  • Kim GA, Lim YS, Han S, Choi J, Shim JH, Kim KM, Lee HC, Lee YS. High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B. Gut. 2018 May;67(5):945-952. doi: 10.1136/gutjnl-2017-314904. Epub 2017 Oct 21.

    PubMed 29055908

  • Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73. doi: 10.1001/jama.295.1.65.

    PubMed 16391218

  • Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ; Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-In HBV (the REVEAL-HBV) Study Group. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006 Mar;130(3):678-86. doi: 10.1053/j.gastro.2005.11.016.

    PubMed 16530509

  • Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, Sun Y, Xuan SY. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011 Mar;53(3):726-36. doi: 10.1002/hep.24105. Epub 2011 Feb 11.

    PubMed 21319189

  • Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, S Sulkowski M, Torriani FJ, Dieterich DT, Thomas DL, Messinger D, Nelson M; APRICOT Clinical Investigators. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006 Jun;43(6):1317-25. doi: 10.1002/hep.21178.

    PubMed 16729309

  • Lim YS, Yu ML, Choi J, Chen CY, Choi WM, Kang W, Kim GA, Kim HJ, Lee YB, Lee JH, Park NH, Kwon SY, Park SY, Kim JH, Choi GH, Jang ES, Chen CH, Hsu YC, Bair MJ, Cheng PN, Tung HD, Chang TS, Lo CC, Tseng KC, Yang SS, Peng CY, Han S. Early antiviral treatment with tenofovir alafenamide to prevent serious clinical adverse events in adults with chronic hepatitis B and moderate or high viraemia (ATTENTION): interim results from a randomised controlled trial. Lancet Gastroenterol Hepatol. 2025 Apr;10(4):295-305. doi: 10.1016/S2468-1253(24)00431-X. Epub 2025 Feb 3.

    PubMed 39914435

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Tenofovir Alafenamide in people with Chronic Hepatitis b, run by Young-Suk Lim 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?

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?

the occurrence of composite events during follow-up observation (time frame: At year 4). 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 NCT03753074, which also lists 14 linked publications.

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.

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