Three Types of Nucleotide/Nucleoside Analogues Therapy in Patients With Hepatitis b Virus Related Compensated Cirrhosis

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 hepatitis b virus related compensated cirrhosis.

Detailed Description
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Hepatitis b virus infection 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 hepatitis b virus related compensated cirrhosis. This study is to investigate the clinical efficacy and safety of three types of nucleotide/nucleoside analogues in treatment of hepatitis b virus related compensated cirrhosis.

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

Conditions
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Hepatitis B, Compensated Cirrhosis

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; Hepatitis b virus DNA positive; Cirrhosis or portal hypertension is found through ultrasonography, computed tomography or magnetic resonance imaging; Do not receive nucleotide/nucleoside analogues treatment in the past half year. Exclusion Criteria: Complications of decompensated cirrhosis: ascites, gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome, etc; 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 |
| --- | --- |
| Active Comparator: ETV group<br>50 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;|
| Active Comparator: TDF group<br>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<br>* Patients would receive treatment of oral tenofovir disoproxil fumarate (TDF) 300 mg once per day.<br>* Other names: Viread;|
| Experimental: TAF group<br>50 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 |
| --- | --- | --- |
| Incidence of decompensated cirrhosis | Incidence of decompensated cirrhosis is evaluated 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 | 
| Ratio of patients with hepatitis b virus e antigen seroconversion after treatment | Hepatitis b virus e antigen and e antibody would be tested to know the ratio of patients with hepatitis b virus e antigen seroconversion at 7 time points after treatment. | 4 week, 8 week, 12 week, 24 week, 48 week, 72 week,144 week | 
| Ratio of patients with undetectable hepatitis b virus surface antigen after treatment | Hepatitis b virus surface antigen would be tested to know the ratio of patients with undetectable hepatitis b virus surface antigen at 7 time points after treatment. | 4 week, 8 week, 12 week, 24 week, 48 week, 72 week,144 week | 
| Serum calcium | Hypocalcemia would be evaluated after treatment | 4 week, 8 week, 12 week, 24 week, 48 week, 72 week,144 week | 
| Serum phosphorus | Hypophosphatemia would be evaluated after treatment | 4 week, 8 week, 12 week, 24 week, 48 week, 72 week,144 week | 
| Blood urea nitrogen | Blood urea nitrogen would be tested after treatment | 4 week, 8 week, 12 week, 24 week, 48 week, 72 week,144 week | 
| Serum creatinine | Serum creatinine would be tested after treatment | 4 week, 8 week, 12 week, 24 week, 48 week, 72 week,144 week | 
| Estimated glomerular filtration rate | Estimated glomerular filtration rate would be evaluated after treatment | 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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nucleoside, hepatitis b virus, compensated cirrhosis, nucleotide