The Efficacy and Safety of TAF vs Other NAs in Patients With LVL

Study Overview
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Brief Summary
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Patients with chronic hepatitis B should maximize the inhibition of HBV replication, which could reduce the incidence of liver cancer and liver disease-related complications. However, after 96 weeks of treatment with the first-line drugs, entecavir or tenofovir disoproxil fumarate, a certain proportion of patients still had low levels of HBV replication. Tenofovir alafenamide fumarate is a newly marketed anti-hepatitis B drug that is currently considered to be non-inferior to tenofovir disoproxil fumarate and safer bone and renal effects. Therefore, this research was put forward to investigate whether tenofovir alafenamide fumarate replacement for hepatitis B had a higher virological response rate and safety in patients with low levels of virus after 48 weeks of treatment with entecavir and tenofovir disoproxil fumarate.

Detailed Description
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Patients who meet the inclusion and exclusion criteria will be enrolled into the research. The participants will voluntarily choose to enter the experimental group or the control group with full informed consent. The control group will continue with the original regimen, while the study group will switch to tenofovir alafenamide fumarate antiviral therapy. Each group will enroll 100 participants.

Official Title
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The Efficacy and Safety of Tenofovir Alafenamide Fumarate Compared With Other Nucleoside Analogues (Acid) to Treat Patients With Low-level Viremia of HBV

Conditions
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Chronic Hepatitis b, Cirrhosis Due to Hepatitis B

Intervention / Treatment
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* Drug: Tenofovir alafenamide fumarate
* Drug: Entecavir or Tenofovir disoproxil fumarate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HBsAg positive for over half a year; Age from 18 to 80 years old; Entecavir (0.5mg qd) or Tenofovir disoproxil fumarate (300mg qd) for 48 weeks or more; HBV DNA level was between 20IU/ ml-2000 IU /mL (COBAS, Taqman). Exclusion Criteria: Low-level viremia of HBV caused by non-standard medication; serum total bilirubin is more than 2 times the upper limit of normal (ULN), or ALT or AST is more than 5ULN, or serum albumin is less than 30g/L; Overlap with HAV, HCV, HDV, HEV or HIV infection; Other liver disease: drug liver disease, alcoholic liver disease, autoimmune liver disease, genetic metabolic liver disease, etc.; Decompensated cirrhosis or liver cancer; Kidney damage, or autoimmune disease, or other organ failure; Combination of Entecavir or Tenofovir disoproxil fumarate ; Interferon therapy within half a year; Entecavir (0.5mg qd) or Tenofovir disoproxil fumarate; Investigator considering inappropriate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: switch to tenofovir alafenamide fumarate<br>Patients will switch to tenofovir alafenamide fumarate treatment, 25mg，once a day | Drug: Tenofovir alafenamide fumarate<br>* Patients would take tenofovir alafenamide fumarate, 25mg，once per day<br>* Other names: Vemlidy;|
| Active Comparator: Continue with the original regimen<br>Patients will continue with the original regimen treatment, entecavir, 0.5mg once a day, or tenofovir disoproxil fumarate 300mg once a day | Drug: Entecavir or Tenofovir disoproxil fumarate<br>* Patients would take entecavir 0.5 mg once per day, or tenofovir disoproxil fumarate 300 mg once per day<br>* Other names: Baraclude or Viread;|

What is the study measuring?
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Primary 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 24 week after treatment. | 24 week | 
| The changes of glomerular filtration rate | Glomerular filtration rate will be tested to know the changes after treatment | 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week | 
| The changes of bone mineral density in lumbar spine and hip | Bone mineral density in lumbar spine and hip were tested after treatment | 0 week, 48 week, 96 week, 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 at 6 time points. | 12 week, 48 week, 72 week, 96 week, 120 week, 144 week | 
| The changes of HBsAg | The levels of HBsAg were tested at each time point. | 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week | 
| The changes of the degree of liver fibrosis | Fibroscan would be conducted once every 48 weeks | 0 week, 48 week, 96 week, 144 week. | 
| Differences in symptoms | Symptoms would be evaluated at each time point | 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week | 
| The changes of HBeAg | The levels of HBeAg were tested at each time point. | 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week | 
| The changes of alanine aminotransferase | The levels of alanine aminotransferase were tested at each time point. | 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week | 
| Differences in body weight | Body weight would be evaluated at each time point | 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week | 
| Differences in proteinuria, albuminuria and urinary β2-microglobulin | Proteinuria, albuminuria and urinary β2-microglobulin would be evaluated at each time point | 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week | 
| Differences in osmotic pressure | The levels of osmotic pressure would be evaluated at each time point | 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week | 
| Differences in blood calcium and phosphorus | The levels of blood calcium and phosphorus would be evaluated at each time point | 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week | 
| Differences in blood lipid | The levels of blood lipid would be evaluated at each time point | 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week | 
| Differences in serum creatine kinase | The levels of creatine kinase would be evaluated at each time point | 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week |