The Efficacy and Safety of Nucleos(t)Ide Analogues in the Treatment of HBV-related Acute-on-chronic Liver Failure
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03640728|
Recruitment Status : Recruiting
First Posted : August 21, 2018
Last Update Posted : May 6, 2019
|Condition or disease||Intervention/treatment|
|Hepatitis B Virus Diseases Liver Failure||Drug: Tenofovir Alafenamide Drug: Entecavir Drug: Tenofovir disoproxil fumarate|
Potent antivirals like entecavir (ETV), Tenofovir Disoproxil Fumarate (TDF) and Tenofovir alafenamide (TAF) now are recommended as first-line therapy for patients with chronic HBV infection because of their significant suppression of viral replication and a high barrier to resistance. HBV-related acute-on-chronic liver failure (ACLF) is a clinical syndrome defined as acute hepatic insult with diagnosed or undiagnosed chronic liver disease. Only a limited number of medical treatments are available for ACLF. Although liver transplantation is a life-saving treatment for ACLF, the difficulty in finding a suitable donor and the high cost hinder its extensive clinical use.
The precise mechanism underlying the liver injury caused by HBV-related ACLF and the factors contributing to the progression of liver failure remain unknown. HBV DNA replication is one of the key factors causing the progression from liver damage to liver failure. Current clinical guidelines advocate oral antiviral treatment in HBV-related ACLF. However, the specific antiviral treatment for patients with liver failure remains unclear. In the past years, efficacy of nucleoside analogues, such as lamivudine, entecavir, telbivudine and tenofovir, for HBV-related liver failure has been reported. However, no conclusion on which nucleoside analogue is the most satisfactory drug for the treatment of HBV-related liver failure has not been reached yet.
In this cohort study, the investigators will compare the efficacy, safety, and tolerability of tenofovir alafenamide (TAF), Tenofovir Disoproxil Fumarate (TDF) and entecavir (ETV) in HBV-related ACLF in China.
|Study Type :||Observational|
|Estimated Enrollment :||200 participants|
|Official Title:||A Multicenter Controlled Open-label Trial of Evaluating Tenofovir Alafenamide, Tenofovir Disoproxil Fumarate and Entecavir in Acute-on-chronic Liver Failure of Chronic Hepatitis B Patients|
|Actual Study Start Date :||January 25, 2019|
|Estimated Primary Completion Date :||April 2021|
|Estimated Study Completion Date :||July 2022|
patients receive entecavir 0.5 mg/day orally.
Entecavir 0.5 mg/day orally
patients receive Tenofovir Disoproxil Fumarate 300 mg/day orally.
Drug: Tenofovir disoproxil fumarate
Tenofovir Disoproxil Fumarate 300 mg/day orally
patients receive Tenofovir alafenamide 25 mg/day orally.
Drug: Tenofovir Alafenamide
Tenofovir alafenamide 25 mg/day orally
- Overall survival of ACLF subjects [ Time Frame: study day 1 through week 48 ]Overall survival in subjects with acute-on-chronic liver failure will be summarized and compared with control subjects through study day 28 and week 48.
- Changes in serum HBV DNA levels [ Time Frame: at week 4 and 48 of treatment ]
- Proportion of patients with hepatitis B e-Ag(HBe-Ag) loss or seroconversion [ Time Frame: at week 4 and 48 of treatment ]
- Proportion of patients with HBs-Ag loss or seroconversion [ Time Frame: at week 4 and 48 of treatment ]
- Proportion of patients with normal alanine aminotransferase(ALT) [ Time Frame: at week 4 and 48 of treatment ]
- Liver function evaluation through Model for End-Stage Liver Disease (MELD) scores [ Time Frame: at week 4 and 48 of treatment ]Model for End-Stage Liver Disease(MELD) Score is calculated according to the equation:3.78×ln[serum bilirubin (mg/dl)] + 11.2×ln(INR) + 9.57×ln[serum creatinine (mg/dL)] + 6.43. Liver function improvement defined as the decline of total MELD score, whereas liver function deterioration defined as the rise of total MELD score. The risk of death increased when total MELD score above 25.
- Proportion of patients with virologic breakthrough [ Time Frame: at week 4 and 48 of treatment ]Virologic breakthrough is defined as the increase in serum HBV DNA by >1 log10 (10-fold) above nadir after achieving virologic response as determined by at least 2 consecutive measurements of at least 2 weeks apart, during continued treatment
- Proportion of patients with complete virologic response [ Time Frame: at week 4 and 48 of treatment ]Virologic response is defined as the serum HBV DNA concentrations below 20 IU/mL
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): NCT03640728
|Contact: Juan Li, M.D.||email@example.com|
|Contact: Yingli He, M.D.,Ph.Dfirstname.lastname@example.org|
|Ankang Central Hospital||Recruiting|
|Hanzhong 3201 Hospital||Not yet recruiting|
|Hanzhong Infectious Hospital||Not yet recruiting|
|Weinan Central Hospital||Not yet recruiting|
|First Affiliated Hospital Xi'an Jiaotong University||Recruiting|
|Shaanxi provincial people's hospital||Not yet recruiting|
|Tangdu Hospital, The Fourth Military Medical University,||Not yet recruiting|
|The Second Affiliated Hospital of Xi'an Jiaotong University||Recruiting|
|Xi'an Central Hospital||Active, not recruiting|
|Xijing Hospital, The Fourth Military Medical University||Not yet recruiting|
|The Affiliated Hospital of Yan'an University||Not yet recruiting|
|Principal Investigator:||Yingli He, M.D.,Ph.D||First Affiliated Hospital Xi'an Jiaotong University|