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Effectiveness of Antiviral Treatment in Cirrhotic Patients With Low-level Hepatitis B Virus DNA Levels (ATTACH)

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ClinicalTrials.gov Identifier: NCT04780204
Recruitment Status : Not yet recruiting
First Posted : March 3, 2021
Last Update Posted : March 4, 2021
Sponsor:
Collaborator:
National Evidence-Based Healthcare Collaborating Agency
Information provided by (Responsible Party):
Young-Suk Lim, Asan Medical Center

Brief Summary:

Multicenter, Open-label, Randomized Controlled Trial Male and female adults with liver cirrhosis due to chronic hepatitis B virus infection who have low-level viremia and are beyond treatment indications by current guidelines.

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 beyond treatment indications by current guidelines, compared with best supportive care


Condition or disease Intervention/treatment Phase
Hepatitis B, Chronic Drug: Treatment Drug: Observation of Hepatitis B Phase 4

Detailed Description:

This clinical trial is a multicenter, open label, randomized controlled study in cirrhotic chronic hepatitis B patients with low-level viremia beyond treatment indications by current guidelines.

Approximately 400 subjects meeting eligibility criteria will be enrolled and randomized (1:1) to Treatment Arm (A) or Observational Arm (B), as below:

  • Treatment Arm (A): 200 subjects, TAF 25mg once daily with food for 3 years
  • Observational Arm (B): 200 subjects, best supportive care for 3 years This study was designed to randomly assign treatment groups to subjects in order to prevent biases that may be intervened, and to increase comparability between the groups. Since HBeAg status could affect the clinical outcome in the eligible subjects, randomization will be stratified by HBeAg status (positive or negative) at screening at a 1:1 ratio by using centralized stratified block randomization.

Both groups (i.e. Treatment Arm and Observational Arm) are scheduled to be followed up to 3 years. When subjects in the Observational Arm group meets the treatment indications by current guidelines (HBV DNA ≥2,000 IU/mL or progressed to decompensated cirrhosis with detectable HBV DNA level), antiviral treatment will be initiated.

The primary endpoint will be analyzed with Kaplan-Meier methods and compared by the log-rank test between the two groups. Between-group comparisons of continuous or categorical baseline characteristics will be conducted using Student's t-test, Chi-square test or Fisher's exact test, as appropriate.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Randomized Controlled Trial for the Effectiveness of Antiviral TreAtment in Cirrhotic Patients With Low-level Hepatitis B Virus DNA Levels (ATTACH)
Estimated Study Start Date : August 2021
Estimated Primary Completion Date : June 2025
Estimated Study Completion Date : December 2025


Arm Intervention/treatment
Experimental: Antiviral Treatment
Tenofovir Alafenamide 25mg once daily , Oral
Drug: Treatment
Tenofovir Alafenamide 25 mg oral once daily
Other Name: Tenofovir alafenamide

Observation
Best supportive care
Drug: Observation of Hepatitis B
Best Supportive care




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Cumulative incidence [ Time Frame: From randomization the composite clinical events will be collected every 1year , assessed up to 3years ]
    death, hepatocellular carcinoma , Liver transplantation, decompensated liver cirrhosis



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Willing and able to provide written informed consent prior to study entry
  2. Age ≥40 years and ≤80 years at the time of screening
  3. 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 (-)
  4. Either HBeAg (+) or HBeAg (-)
  5. Serum HBV DNA levels ≥20 IU/mL and <2,000 IU/mL at the time of screening
  6. Evidence of liver cirrhosis defined as meeting any of the following criteria:

    • 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)
  7. Estimated creatinine clearance ≥30 ml/min (by calculation of creatinine clearance or using the CKD-EPI equation)
  8. Ability to comply with all study requirements

Exclusion Criteria:

  1. Confirmed known co-infection with HCV, HIV, or HDV
  2. Current alcohol (60g/day) or substance abuse judged by the investigator that will potentially interfere with subject compliance
  3. 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
  4. Currently on or have received therapy with Interferon or immunosuppressant (including systemic chemotherapy) within 12 months prior to the screening
  5. 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
  6. Received solid organ or bone marrow transplant
  7. History of severe, life-threatening or other significant sensitivity to any excipients of the study drugs
  8. 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.
  9. Currently on or have received antiviral treatment for ≥ 2 weeks within 6 months prior to the screening
  10. 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)
  11. 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.
  12. 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.
  13. Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04780204


Contacts
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Contact: Young-Suk Lim, PhD 82-2-3010-3190 limys@amc.seoul.kr

Sponsors and Collaborators
Asan Medical Center
National Evidence-Based Healthcare Collaborating Agency
Investigators
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Principal Investigator: Young-Suk Lim, PhD Asan Medical Center
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Responsible Party: Young-Suk Lim, PhD, Asan Medical Center
ClinicalTrials.gov Identifier: NCT04780204    
Other Study ID Numbers: IN-KR-320-6132
First Posted: March 3, 2021    Key Record Dates
Last Update Posted: March 4, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Tenofovir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents