Tenofovir Versus Lamivudine for Patients of Chronic Hepatitis B With Severe Acute Exacerbation

Study Overview
=================
Brief Summary
-----------------
In Taiwan, 15% of general population had hepatitis B virus (HBV) infection, HBV is the leading cause of liver cirrhosis and hepatocellular carcinoma in Taiwan. After entering immune clearance, 10-30% of patients of chronic HBV develop acute exacerbation (AE) , some are mild but some developed hepatic decompensation or even death. Previous study found that early use of lamivudine before bilirubin level is above 20 mg/dl can improve survival in chornic HBV with severe AE. From the study from Hongkong, lamivudine was found to have better survival than entecavir in chronic HBV with severe AE. Recent study from India found that tenofovir is able to improve survival in chronic HBV with severe AE. The aim of this study is to compare the effect of lamivudine and tenofovir for chronic HBV with severe AE. The study aims to enroll 120 patients with chronic HBV defined as persistence of HBsAg for more than 6 months. Severe AE was defined as ALT > 400 U/L, prolongation of prothrombin time > 3 seconds, bilirubin > 2 mg/dl. Patients with hepatitis A, C, D or HIV infection, drug or alcoholic liver disease, hepatocellular carcinoma, under immuno-suppressive agents use, or previous use of anti-HBV agents are excluded. All enrolled patients are randomized into group A who received tenofovir 300 mg qd for 3 years and group B who received lamivuidne 100 mg qd for 6 months, followed by tenofovir 300mg qd for 30 months. Mortality rate and virological, biochemical and serological response were evaluated at 1,2,4,48,96 and 144 weeks. The values are expressed as mean + SD. Categorical variables were analyzed with Chi-square test or Fisher's exact test as appropriate and continuous variables were analyzed by Mann-Whitney test. Logistic regression test was applied to analyze the independent association of various variables with outcome. A p value < 0.05 was regarded as significant.

Official Title
-----------------
Tenofovir Versus Lamivudine for Patients of Chronic Hepatitis B With Severe Acute Exacerbation

Conditions
-----------------
Chronic HBV With Severe Exacerbation

Intervention / Treatment
-----------------
* Drug: Tenofovir
* Drug: lamivudine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HBsAg (+) > 6 months ALT > 5X ULN Prolongation of prothrombin time > 3 seconds and bilirubin level > 2 mg/dl 20-75 years old Exclusion Criteria: HAV, HCV, HDV and HIV co-infection Concurrent hepatocellular carcinoma Drug, metabolic or alcohol as cause of hepatitis Anti-viral treatment in recent 6 mnths Pregnant woman

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tenofovir<br>All enrolled patients are randomized to tenofovir arm who receives tenofovir 300 mg qd for 36 months | Drug: Tenofovir<br> <br> * Other names: viread;|
| Placebo Comparator: lamivudine<br>All enrolled patients are randomized to lamivudine arm who received lamivudine 100 mg qd for 6 months, followed by tenofovir for another 30 months. | Drug: lamivudine<br> <br> * Other names: zeffix;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 months survival | 6 months survival after treatment begins | 6 months after treatment begins | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rapid virological response | Evaluate the relationship of rapid virological response ( at 1,2 and 4 weeks) and survival | 1,2 and 4 weeks after treatment | 
| HBeAg seroconversion and virological response 1, 2, and 3 years after treatment | To evaluate the rate of HBeAg seroconversion and virological response 1, 2, and 3 years after treatment in the two arms | 1,2 and 3 years after treatment | 
| Safety profile | Number of Participants with Adverse Events as a Measure of Safety and Tolerability | during and 6 months after treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
tenofovir, lamivudine, hepatitis B, acute exacerbation