Antiviral Therapy for Patients With Chronic Hepatitis B Infection

Study Overview
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Brief Summary
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The study aims to demonstrate that antiviral therapy for patients with immune tolerance of CHB. On the basis of the original antiviral therapy of entecavir, further clarify the safety and effectiveness of entecavir combined with tenofovir amibufenamide.The investigators plan to enroll about 328 hepatitis B patients,. who are in the stage of immune tolerance. These participants will be devided into two groups randomly .Group A will receive the treatment of entecavir. Group B will be treated with entecavir and tenofovir amibufenamide. The participants in both groups will be followed up for 96 weeks. The primary endpoint is to compare the inhibition rate of HBV-DNA between two groups. The secondary endpoint includes: (1) Comparing the decrease of HBV DNA at 48 weeks between the two groups. (2) Comparing the HBeAg seroconversion rates at 48 weeks and 96 weeks between the two groups. (3) The changes of HBsAg at 48 weeks and 96 weeks between the two groups. (4) Comparing adverse side effects between the two groups.

Detailed Description
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High HBV DNA level is an independent risk factor for liver cirrhosis and liver cancer, we know all patients with chronic hepatitis B virus infection in immune tolerance period had high viral load. So it is necessary to implement antiviral therapy for patients with chronic hepatitis B virus infection in immune tolerance period.Previous studies have found that combination of two antiviral drugs has a higher virological inhibition rate in patients with high viral load than single drug. Hence, the investigators' hypothesis is that treatment of patients with chronic hepatitis B virus infection in immune tolerance period result in higher virological inhibition rate and reduce of the risk of cirrhosis and liver cancer. The investigators plan to enroll about 328 hepatitis B patients, who are in the stage of immune tolerance. These participants will be devided into 2 groups.Group A will receive the treatment of entecavir . Group B will be treated with entecavir and tenofovir amibufenamide. The participants in both groups will be followed up for 96 weeks. Unless there are serious adverse drug reactions, the protocol cannot be adjusted within 96 weeks. The primary endpoint is to compare the inhibition rate of HBV-DNA between two groups. The secondary endpoint includes: (1) Comparing the decrease of HBV DNA at 48 weeks between the two groups. (2) Comparing the HBeAg seroconversion rates at 48 weeks and 96 weeks between the two groups. (3) The changes of HBsAg at 48 weeks and 96 weeks between the two groups. (4) Comparing adverse side effects between the two groups.

Official Title
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Exploratory Study on Antiviral Therapy for Patients With Chronic Hepatitis B Virus Infection (Immune Tolerance Period)

Conditions
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Chronic Hepatitis B Virus Infection

Intervention / Treatment
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* Drug: Entecavir
* Drug: Entecavir combined with Tenofovir Amibufenamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18-65 years old; HBsAg positive >6 months, HBsAg>1*10e4IU/ml; HBV-DNA> 2 * 10e7IU / ml; HBeAg positive; ALT / AST remained normal which were followed up twice within 1 year with at least a 6-month interval each time. No antiviral treatment with interferon or nucleoside (acid) analogues in the previous year Exclusion Criteria: infection with hepatitis A, C, D, E viruses or HIV infection ; Combined with diabetes, hypertension, renal insufficiency, autoimmune diseases and other organ dysfunction And malignant tumors; Patients using Immunosuppressive therapy or radiotherapy / chemotherapy for other diseases; Patients with liver fibrosis, cirrhosis (FibroScan > = 9.4kpa) and liver cancer were identified; Extrahepatic manifestations related to HBV (glomerulonephritis, vasculitis, nodular polyarteritis, peripheral neuropathy, etc.); Allergic to nucleoside drugs Pregnancy or having pregnancy plan within 2 years and Lactating patients; Patients who are unable to comply with the arrange ment of this study or sign the informed consent. Failed to return to hospital regularly for follow-up ac- cording to the study plan. Researchers determine other condition that does not fit into the study.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Entecavir group<br>Patients receive treatment with entecavir | Drug: Entecavir<br>* Entecavir group will receive entecavir orally once a day, 0.5mg each time, and fasting for 2h before and after taking the medicine<br>* Other names: Boludine/Rui fu en;|
| Experimental: Entecavir and Tenofovir Amibufenamide group<br>Patients will receive the treatment of entecavir combined with tenofovir amibufenamide | Drug: Entecavir combined with Tenofovir Amibufenamide<br>* Entecavir combined with Tenofovir Amibufenamide group will be treated with entecavir and tenofovir amibufenamide. Entecavir is administered in the same way as before. enofovir amibufenamide orally 25mg once a day with meals<br>* Other names: Heng mu;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The inhibition rate of HBV-DNA between two groups | compare the inhibition rate of HBV-DNA between two groups at 96 weeks | 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The decrease of HBV DNA in the at 48 weeks between the two groups | comparing the decrease of HBV DNA in the at 48 weeks between the two groups | 48 weeks | 
| The HBeAg seroconversion rates at 48 weeks and 96 weeks | comparing the HBeAg seroconversion rates at 48 weeks and 96 weeks between the two groups | 48 weeks and 96 weeks | 
| The changes of HBsAg | The changes of HBsAg at 48 weeks and 96 weeks were compared between the two groups | 48 weeks and 96 weeks | 
| adverse side effects | comparing adverse side effects between the two groups | 4、12、24、48、72 and 96 weeks |