ATTACH: Effectiveness of Antiviral Treatment in Cirrhotic Patients With Low-level Hepatitis B Virus DNA Levels
Study Details
Study Description
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 |
|---|---|---|
|
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:
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Treatment Arm (A): 200 subjects, TAF 25mg once daily with food for 3 years
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Antiviral Treatment Tenofovir Alafenamide 25mg once daily , Oral |
Drug: Treatment
Tenofovir Alafenamide 25 mg oral once daily
Other Names:
|
| Other: Observation Best supportive care |
Drug: Observation of Hepatitis B
Best Supportive care
|
Outcome Measures
Primary Outcome Measures
- cumulative incidence rate of composite clinical events [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
- Cumulative incidence [From randomization the composite clinical events will be collected every 1year , assessed up to 3years]
death, hepatocellular carcinoma , Liver transplantation, decompensated liver cirrhosis
Eligibility Criteria
Criteria
Inclusion Criteria:
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Willing and able to provide written informed consent prior to study entry
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Age ≥30 years and ≤80 years at the time of screening
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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 (-)
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Either HBeAg (+) or HBeAg (-)
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Serum HBV DNA levels ≥20 IU/mL and <2,000 IU/mL at the time of screening
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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
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Platelet count <150,000 /mm3
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Presence of esophageal or gastric varices by endoscopy in 2 years before the timing of screening
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Clinically significant portal hypertension
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Fibroscan ≥12.0 kPa (if the test was done in 6 months before the time of screening)
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Estimated creatinine clearance ≥30 ml/min (by calculation of creatinine clearance or using the CKD-EPI equation)
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Ability to comply with all study requirements
Exclusion Criteria:
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Confirmed known co-infection with HCV, HIV, or HDV
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Current alcohol (60g/day) or substance abuse judged by the investigator that will potentially interfere with subject compliance
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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
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Currently on or have received therapy with Interferon or immunosuppressant (including systemic chemotherapy) within 12 months prior to the screening
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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
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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
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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.
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Currently on or have received antiviral treatment for ≥ 2 weeks within 6 months prior to the screening
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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)
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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.
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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.
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Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Kyungpook National University Hospital | Daegu | Korea, Republic of | ||
| 2 | Asan Medical Center | Seoul | Korea, Republic of | ||
| 3 | Chung-Ang University Hospital | Seoul | Korea, Republic of | ||
| 4 | Konkuk University Hospital | Seoul | Korea, Republic of | ||
| 5 | Korea University Guro Hospital | Seoul | Korea, Republic of | ||
| 6 | Kyung-Hee University Hospital | Seoul | Korea, Republic of | ||
| 7 | Samsung Medical center | Seoul | Korea, Republic of | ||
| 8 | Seoul National University Hospital | Seoul | Korea, Republic of | ||
| 9 | The Catholic University of Korea, Seoul ST. Mary's Hospital | Seoul | Korea, Republic of | ||
| 10 | Ulsan University Hospital | Ulsan | Korea, Republic of |
Sponsors and Collaborators
- Asan Medical Center
- National Evidence-Based Healthcare Collaborating Agency
Investigators
- Principal Investigator: Young-Suk Lim, PhD, Asan Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IN-KR-320-6132