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

December 12, 2024 updated by: Young-Suk Lim

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
780

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Korea, Republic of
      • Daegu, Korea, Republic of
        • Kyungpook National University Hospital
      • Seongnam, Korea, Republic of
        • Seoul National University Bundang Hospital
      • Seoul, Korea, Republic of
        • Seoul National University Hospital
      • Seoul, Korea, Republic of
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center
      • Seoul, Korea, Republic of
        • Chung-Ang University Hospital
      • Seoul, Korea, Republic of
        • Korea University Guro Hospital
      • Seoul, Korea, Republic of
        • Konkuk University Hospital
      • Seoul, Korea, Republic of
        • Kyung-Hee University Hospital
      • Ulsan, Korea, Republic of
        • Ulsan University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

5. Received interferon or other immunomodulatory treatment for HBV infection in the 12 months before screening for this study

6. Medical condition that requires concurrent use of systemic corticosteroid or other immunosuppressive agents

7. Received solid organ or bone marrow transplant

8. Known hypersensitivity to study drugs, metabolites, or formulation excipients

9. 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

10. Use of investigational agents within 6 months of screening, unless allowed by the Sponsor or Investigator

11. Significant renal, cardiovascular, pulmonary, or neurological disease in the opinion of the Investigator

12. 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

13. Pregnant or breastfeeding or willing to be pregnant

14. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment Arm A (TAF)
390 subjects administered Tenofovir Alafenamide 25 mg once daily
Drug: Tenofovir Alafenamide
Tenofovir Alafenamide 25mg, Tablet, Oral, Daily
Other Names:
  • Vemlidy
No Intervention: Treatment Arm B (Best supportive care)

390 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 the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
the occurrence of composite events during follow-up observation
Time Frame: At year 4
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
At year 4

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cumulative rate of patients with clinical events
Time Frame: At year 4, 8 and 12
Cumulative rate of patients with clinical events (death, liver transplantation, liver decompensation, portal hypertensive complications, and HCC)
At year 4, 8 and 12
Cumulative incidence rate of HCC
Time Frame: At year 4, 8 and 12
Cumulative incidence rate of HCC
At year 4, 8 and 12
All-cause mortality
Time Frame: At year 4, 8 and 12
All-cause mortality
At year 4, 8 and 12
Cumulative incidence rate of liver transplantation
Time Frame: At year 4, 8 and 12
Cumulative incidence rate of liver transplantation
At year 4, 8 and 12
Cumulative incidence rate of liver decompensation
Time Frame: At year 4, 8 and 12
Cumulative incidence rate of liver decompensation
At year 4, 8 and 12
Cumulative incidence rate of portal hypertensive complications
Time Frame: At year 4, 8 and 12
Cumulative incidence rate of portal hypertensive complications
At year 4, 8 and 12
Rate of receiving nucleos(t)ide analogue by meeting reimbursement criteria of treatment among Treatment ARM B subjects
Time Frame: At year 4, 8 and 12
Rate of receiving nucleos(t)ide analogue by meeting reimbursement criteria of treatment among Treatment ARM B subjects
At year 4, 8 and 12
Virologic response defined as HBV DNA less than 15 IU/mL
Time Frame: At year 4, 8 and 12
Virologic response defined as HBV DNA less than 15 IU/mL
At year 4, 8 and 12
Rate of ALT normalization
Time Frame: At year 4, 8 and 12
Rate of ALT normalization if baseline ALT is elevated
At year 4, 8 and 12
Rate of HBeAg seroclearance and seroconversion
Time Frame: At year 4, 8 and 12
Rate of HBeAg seroclearance and seroconversion among HBeAg-positive patients
At year 4, 8 and 12
Change of fibroscan
Time Frame: At year 4, 8 and 12
Change of fibroscan
At year 4, 8 and 12
Change of APRI index
Time Frame: At year 4, 8 and 12
Change of APRI index
At year 4, 8 and 12
Change of FIB-4
Time Frame: At year 4, 8 and 12
Change of FIB-4
At year 4, 8 and 12
Cumulative incidence rate of HCC among HBeAg-positive or HBeAg-negative Patients
Time Frame: At year 4, 8 and 12
Cumulative incidence rate of HCC among HBeAg-positive or HBeAg-negative Patients
At year 4, 8 and 12
All cause-mortality among HBeAg-positive or HBeAg-negative
Time Frame: At year 4, 8 and 12
All cause-mortality among HBeAg-positive or HBeAg-negative
At year 4, 8 and 12
Cumulative incidence rate of liver transplantation among HBeAg-positive or HBeAg-negative
Time Frame: At year 4, 8 and 12
Cumulative incidence rate of liver transplantation among HBeAg-positive or HBeAg-negative
At year 4, 8 and 12
Cumulative incidence rate of liver decompensation among HBeAg-positive or HBeAg-negative
Time Frame: At year 4, 8 and 12
Cumulative incidence rate of liver decompensation among HBeAg-positive or HBeAg-negative
At year 4, 8 and 12
Cumulative incidence rate of portal hypertensive complications among HBeAg-positive or HBeAg-negative
Time Frame: At year 4, 8 and 12
Cumulative incidence rate of portal hypertensive complications amongHBeAg-positive or HBeAg-negative
At year 4, 8 and 12
Cumulative incidence rate of HCC among subjects according to baseline ALT level (normal ALT and elevated ALT)
Time Frame: At year 4, 8 and 12
Cumulative incidence rate of HCC amongsubjects according to baseline ALT level (normal ALT and elevated ALT)
At year 4, 8 and 12
All cause-mortality among subjects according to baseline ALT level (normal ALT and elevated ALT)
Time Frame: At year 4, 8 and 12
All cause-mortality among subjects according to baseline ALT level (normal ALT and elevated ALT)
At year 4, 8 and 12
Cumulative incidence rate of liver transplantation among subjects according to baseline ALT level (normal ALT and elevated ALT)
Time Frame: At year 4, 8 and 12
Cumulative incidence rate of liver transplantation among subjects according to baseline ALT level (normal ALT and elevated ALT)
At year 4, 8 and 12
Cumulative incidence rate of liver decompensation among subjects according to baseline ALT level (normal ALT and elevated ALT)
Time Frame: At year 4, 8 and 12
Cumulative incidence rate of liver decompensation among subjects according to baseline ALT level (normal ALT and elevated ALT)
At year 4, 8 and 12
Cumulative incidence rate of portal hypertensive complications among subjects according to baseline ALT level (normal ALT and elevated ALT)
Time Frame: At year 4, 8 and 12
Cumulative incidence rate of portal hypertensive complications among subjects according to baseline ALT level (normal ALT and elevated ALT)
At year 4, 8 and 12
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
Time Frame: At year 4, 8 and 12
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
At year 4, 8 and 12
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
Time Frame: At year 4, 8 and 12
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
At year 4, 8 and 12
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
Time Frame: At year 4, 8 and 12
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
At year 4, 8 and 12
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
Time Frame: At year 4, 8 and 12
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
At year 4, 8 and 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Young-Suk Lim

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Samsung Medical Center
Seoul St. Mary's Hospital
China Medical University Hospital
Chang Gung Memorial Hospital
Seoul National University Hospital
Ulsan University Hospital
Seoul National University Bundang Hospital
Korea University Guro Hospital
National Cheng-Kung University Hospital
Kyungpook National University Hospital
Chung-Ang University Hosptial, Chung-Ang University College of Medicine
Kaohsiung Medical University
Konkuk University Medical Center
Taichung Veterans General Hospital
Chiayi Christian Hospital
E-DA Hospital
Chi Mei Medical Hospital
Dalin Tzu Chi General Hospital
Kyunghee University Medical Center
St. Martin De Porress Hospital
Taitung Mackay Memorial Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Young-Suk Lim, M.D, Ph D, Asan Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 18, 2019

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2031

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 22, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 22, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 26, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 12, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IN-KR-320-5358

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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