The Efficacy and Safety of Nucleos(t)Ide Analogues in the Treatment of HBV-related Acute-on-chronic Liver Failure

NCT03640728 | Unknown

• 1 other identifier: XJTU1AF2018LSL-002
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Hepatitis B; Virus Diseases; Liver Failure

Keywords

Hepatitis B, Acute-on-Chronic liver failure

Outcome Measures

Primary Outcomes (1)

• Overall survival of ACLF subjects

  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.

  study day 1 through week 48

Secondary Outcomes (7)

• Changes in serum HBV DNA levels

  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 HBs-Ag loss or seroconversion

  at week 4 and 48 of treatment

• Proportion of patients with normal alanine aminotransferase(ALT)

  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

Study Arms (3)

ETV

patients receive entecavir 0.5 mg/day orally.

Drug: Entecavir

TDF

patients receive Tenofovir Disoproxil Fumarate 300 mg/day orally.

Drug: Tenofovir disoproxil fumarate

TAF

patients receive Tenofovir alafenamide 25 mg/day orally.

Drug: Tenofovir Alafenamide

Interventions

Tenofovir Alafenamide DRUG

Tenofovir alafenamide 25 mg/day orally

TAF

Entecavir DRUG

Entecavir 0.5 mg/day orally

ETV

Tenofovir disoproxil fumarate DRUG

Tenofovir Disoproxil Fumarate 300 mg/day orally

TDF

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

All the patients received antivirals will be followed for at least 48 weeks and follow-up assessments were performed at week 1, 2, 3, 4, 12, 24 and 48.All the patients were detected Serum HBV DNA,HBV markers, including HBsAg, HBsAb, HBeAg, HBeAb and HBcAb, routine biochemical tests mainly including ALT,AST,TB and ALB.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead

Study Sites (11)

Ankang Central Hospital

Ankang, China

RECRUITING

Hanzhong 3201 Hospital

Hanzhong, China

NOT YET RECRUITING

Hanzhong Infectious Hospital

Hanzhong, China

NOT YET RECRUITING

Weinan Central Hospital

Weinan, China

NOT YET RECRUITING

First Affiliated Hospital Xi'an Jiaotong University

Xi'an, China

RECRUITING

Shaanxi provincial people's hospital

Xi'an, China

NOT YET RECRUITING

Tangdu Hospital, The Fourth Military Medical University,

Xi'an, China

NOT YET RECRUITING

The Second Affiliated Hospital of Xi'an Jiaotong University

Xi'an, China

RECRUITING

Xi'an Central Hospital

Xi'an, China

ACTIVE NOT RECRUITING

Xijing Hospital, The Fourth Military Medical University

Xi'an, China

NOT YET RECRUITING

The Affiliated Hospital of Yan'an University

Yan’an, China

NOT YET RECRUITING

Related Publications (1)

• Li J, Hu C, Chen Y, Zhang R, Fu S, Zhou M, Gao Z, Fu M, Yan T, Yang Y, Li J, Liu J, Chen T, Zhao Y, He Y. Short-term and long-term safety and efficacy of tenofovir alafenamide, tenofovir disoproxil fumarate and entecavir treatment of acute-on-chronic liver failure associated with hepatitis B. BMC Infect Dis. 2021 Jun 14;21(1):567. doi: 10.1186/s12879-021-06237-x.

  PMID: 34126939 DERIVED

MeSH Terms

Conditions

Hepatitis B; Virus Diseases; Liver Failure; Acute-On-Chronic Liver Failure

Interventions

tenofovir alafenamide; entecavir; Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatic Insufficiency; Liver Failure, Acute

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Yingli He, M.D.,Ph.D

  First Affiliated Hospital Xi'an Jiaotong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Juan Li, M.D.

CONTACT

18209272726; lijuan1996xx@163.com

Yingli He, M.D.,Ph.D

CONTACT

18991232863; heyingli2000@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: He Yingli, Research Associate

Study Record Dates

• First Submitted: August 19, 2018
• First Posted: August 21, 2018
• Study Start: January 25, 2019
• Primary Completion: April 30, 2021
• Study Completion: July 1, 2023
• Last Updated: February 9, 2023

Record last verified: 2023-02

Locations

CN (11)