Three Types of Nucleotide/Nucleoside Analogues Therapy in Patients With Chronic Hepatitis b

Study Overview
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Brief Summary
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This study is to investigate the clinical efficacy and safety of three types of nucleotide/nucleoside analogues in treatment of chronic hepatitis b

Detailed Description
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Chronic hepatitis b (CHB) remains a serious public health problem 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 CHB. This study is to investigate the clinical efficacy and safety of three types of nucleotide/nucleoside analogues in treatment of CHB.

Official Title
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Study on Therapeutic Effects and Safety of Three Types of Nucleotide/Nucleoside Analogues in Patients With Chronic Hepatitis b

Conditions
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Chronic Hepatitis b

Intervention / Treatment
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* Drug: Entecavir
* Drug: Tenofovir Disoproxil Fumarate
* Drug: Tenofovir Alafenamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive hepatitis b surface antigen or hepatitis b virus DNA > 0.5 year; Age from 18 to 65 years old; HBeAg-positive: HBV DNA≥20000IU/ml，HBeAg-negative: HBV DNA≥2000IU/ml； ALT≥2×ULN； Do not receive nucleotide/nucleoside analogues treatment in the past half year. Exclusion Criteria: Other active liver diseases; Hepatocellular carcinoma or other malignancy; Pregnancy or lactation; Human immunodeficiency virus infection or congenital immune deficiency diseases; Severe diabetes, autoimmune diseases; Other important organ dysfunctions; Using glucocorticoid; Patients can not follow-up; Investigator considering inappropriate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ETV group<br>100 patients would receive treatment of oral entecavir (ETV) 0.5 mg once per day from baseline to life-long. | Drug: Entecavir<br>* Patients would receive treatment of oral entecavir (ETV) 0.5 mg once per day.<br>* Other names: Baraclude;|
| Experimental: TDF group<br>100 patients would receive treatment of oral tenofovir disoproxil fumarate (TDF) 300 mg once per day from baseline to life-long. | Drug: Tenofovir Disoproxil Fumarate<br>* Patients would receive treatment of oral tenofovir disoproxil fumarate (TDF) 300 mg once per day.<br>* Other names: Viread;|
| Experimental: TAF group<br>100 patients would receive treatment of oral tenofovir alafenamide (TAF) 25 mg once per day from baseline to life-long. | Drug: Tenofovir Alafenamide<br>* Patients would receive treatment of oral tenofovir alafenamide (TAF) 25 mg once per day.<br>* Other names: Vemlidy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of renal function decline | Renal function indicators mainly include blood urea nitrogen, serum creatine and estimated glomerular filtration rate, and the rate of renal function decline would be evaluated. | 144 week | 
| Rate of hypercalcemia | The serum calcium would be detected to know the ratio of patients with hypercalcemia. | 144 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hepatitis b virus(HBV) DNA undetectable rate | Hepatitis b virus DNA would not be detected if it below the upper limit of test value. | 0 week, 4 week, 8 week, 12 week, 24 week, 48 week, 72 week,144 week | 
| hepatitis b e antigen loss rate | Hepatitis b e antigen would be tested to know the ratio of patients with negative hepatitis B e antigen. | 0 week, 4 week, 8 week, 12 week, 24 week, 48 week, 72 week,144 week | 
| hepatitis b s antigen loss rate | Hepatitis b s antigen become negative and quantitative analysis below the upper limit of test value. | 0 week, 4 week, 8 week, 12 week, 24 week, 48 week, 72 week,144 week | 
| hepatitis b e antigen seroconversion rate | hepatitis b e antibody would be tested to know the ratio of patients with positive hepatitis B e antibody | 0 week, 4 week, 8 week, 12 week, 24 week, 48 week, 72 week,144 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic hepatitis b, nucleoside, nucleotide