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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 11
- 主要终点
- Overall survival of ACLF subjects
研究概览
简要总结
HBV-related acute-on-chronic liver failure (ACLF) is a clinical syndrome defined as acute hepatic insult with diagnosed or undiagnosed chronic liver disease. Current clinical guidelines advocate oral antiviral treatment in HBV-related ACLF. 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. In addition, the drug metabolism characteristics of TAF will be explored in such severe liver injury population of HBV-ACLF.
详细描述
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. In addition, pharmacokinetic properties of TAF tablets will be explored in the study subjects.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All of below
- •age 18-70 years, male or female.
- •HBsAg positive at least 6 months or more, HBeAg positive or negative.
- •Serum HBV DNA positive (Serum HBV DNA should be determined by the PCR assay at the local laboratory at screening for this study)
- •Recent development of increasing jaundice (a total serum bilirubin concentration of above 85μmol/L) and coagulopathy (INR ≥1.5 or prothrombin activity<40%)
- •Recent development of complications such as hepatic encephalopathy, or abrupt and obvious increase in ascites, or spontaneous bacterial peritonitis, or hepatorenal syndrome.
- •Patient is willing and able to comply with the study drug regimen and all other study requirements.
- •The patient is willing and able to provide written informed consent to participate in the study.
排除标准
- •Any of below
- •Patient has concomitant other chronic viral infection (HCV or HIV)
- •Patient has evidence of renal insufficiency defined as serum creatinine > 1.5 mg/dL
- •Patient has medical condition that requires concurrent use of systemic prednisolone or other immunosuppressive agent (including chemotherapeutic agent)
- •Patient is pregnant or breastfeeding or willing to be pregnant
- •Patient has one or more additional known primary or secondary causes of liver disease, other than hepatitis B (e.g., alcoholism, autoimmune hepatitis, malignancy with hepatic involvement, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's Disease, other congenital or metabolic conditions affecting the liver, congestive heart failure or other severe cardiopulmonary disease, etc.).
- •A history of treated malignancy (other than hepatocellular carcinoma) is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding three years.
- •Active ethanol/drug abuse/psychiatric problems such as major depression, schizophrenia, bipolar illness, obsessive-compulsive disorder, severe anxiety, personality disorder that might interfere with participation in the study.
- •Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance.
研究组 & 干预措施
ETV
patients receive entecavir 0.5 mg/day orally.
干预措施: Entecavir (Drug)
TDF
patients receive Tenofovir Disoproxil Fumarate 300 mg/day orally.
干预措施: Tenofovir disoproxil fumarate (Drug)
TAF
patients receive Tenofovir alafenamide 25 mg/day orally.
干预措施: Tenofovir Alafenamide (Drug)
结局指标
主要结局
Overall survival of ACLF subjects
时间窗: 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.
次要结局
- Proportion of patients with normal alanine aminotransferase(ALT)(at week 4 and 48 of treatment)
- Changes in serum HBV DNA levels(at week 4 and 48 of treatment)
- Proportion of patients with complete virologic response(at week 4 and 48 of treatment)
- Proportion of patients with HBs-Ag loss or seroconversion(at week 4 and 48 of treatment)
- Liver function evaluation through Model for End-Stage Liver Disease (MELD) scores(at week 4 and 48 of treatment)
- Proportion of patients with hepatitis B e-Ag(HBe-Ag) loss or seroconversion(at week 4 and 48 of treatment)
- Proportion of patients with virologic breakthrough(at week 4 and 48 of treatment)
研究者
He Yingli
He Yingli, Research Associate
First Affiliated Hospital Xi'an Jiaotong University