Three Types of Nucleotide/Nucleoside Analogues Treatment in HBV Related ACLF (HBV)

Study on Three Types of Nucleotide/Nucleoside Analogues Treatment in Patients With Hepatitis b Virus Related Acute-on-chronic Liver Failure

This study is to investigate the clinical efficacy of three types of nucleotide/nucleoside analogues in treatment of HBV-related acute-on-chronic liver failure.

Study Overview

• Status: Recruiting
• Conditions: Acute-On-Chronic Liver Failure; Hepatitis B
• Intervention / Treatment: Drug: Entecavir; Drug: Tenofovir Disoproxil Fumarate; Drug: Tenofovir Alafenamide

Detailed Description

Hepatitis b virus (HBV) related acute-on-chronic liver failure (ACLF) is a serious condition with high mortality rate in China. Nucleotide/nucleoside analogues are used for anti-virus treatment in these patients. Entecavir, Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide are first line drug in China. But there still lacks of data of Tenofovir Alafenamide in treatment of HBV related ACLF. This study is to investigate the clinical efficacy of three types of nucleotide/nucleoside analogues in treatment of HBV related ACLF.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • Recruiting
      • Third Affiliated Hospital of Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Positive hepatitis b surface antigen or hepatitis b virus DNA > 0.5 year;
2. Age from 18 to 55 years old;
3. Serum total bilirubin level > 10 times upper limit of normal;
4. Prothrombin time activity < 40% or prothrombin time international ratio > 1.5；
5. Do not receive nucleotide/nucleoside analogues treatment in the past half year.

Exclusion Criteria:

1. Other active liver diseases;
2. Hepatocellular carcinoma or other malignancy;
3. Pregnancy or lactation;
4. Human immunodeficiency virus infection or congenital immune deficiency diseases;
5. Severe diabetes, autoimmune diseases;
6. Other important organ dysfunctions;
7. Using glucocorticoid;
8. Patients can not follow-up;
9. Investigator considering inappropriate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ETV group; 50 patients would receive treatment of oral entecavir (ETV) 0.5 mg once per day from baseline to life-long.	Drug: Entecavir; Patients would receive treatment of oral entecavir (ETV) 0.5 mg once per day.; Other Names: Baraclude
Active Comparator: TDF group; 50 patients would receive treatment of oral tenofovir disoproxil fumarate (TDF) 300 mg once per day from baseline to life-long.	Drug: Tenofovir Disoproxil Fumarate; Patients would receive treatment of oral tenofovir disoproxil fumarate (TDF) 300 mg once per day.; Other Names: Viread
Experimental: TAF group; 50 patients would receive treatment of oral tenofovir alafenamide (TAF) 25 mg once per day from baseline to life-long.	Drug: Tenofovir Alafenamide; Patients would receive treatment of oral tenofovir alafenamide (TAF) 25 mg once per day.; Other Names: Vemlidy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival rate in the follow-up	Whether patients will survive after treatment is observed in the follow-up.	144 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of patients with undetectable hepatitis b virus DNA after treatment	Hepatitis b virus DNA would be tested to know the ratio of patients with undetectable hepatitis b virus DNA at 7 time points after treatment.	4 week, 8 week, 12 week, 24 week, 48 week, 72 week,144 week
Model for end-stage liver disease (MELD) score is recorded after treatment	The calculation of model for end-stage liver disease (MELD) score is: R=0.378ln[serum total bilirubin (mg/dl)]+1.12ln(prothrombin time international normalized ratio)+0.95ln[serum creatinin(mg/dl)]+0.64. The higher the MELD score, the higher the mortality rate. MELD score is recorded after treatment.	0 week, 4 week, 8 week, 12 week, 24 week, 48 week, 72 week,144 week

Collaborators and Investigators

• Sponsor: Third Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Anticipated): October 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: April 16, 2019
• First Submitted That Met QC Criteria: April 17, 2019
• First Posted (Actual): April 19, 2019

Study Record Updates

• Last Update Posted (Actual): April 19, 2019
• Last Update Submitted That Met QC Criteria: April 17, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: nucleotide; acute-on-chronic liver failure; hepatitis b virus; nucleoside
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Liver Failure, Acute; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; End Stage Liver Disease; Liver Failure; Hepatic Insufficiency; Acute-On-Chronic Liver Failure; Hepatitis B; Hepatitis; Hepatitis A; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Entecavir
• Other Study ID Numbers: PL6

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No