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

Kaohsiung Veterans General Hospital

Status and phase: Unknown; Phase 3

Conditions: Chronic HBV With Severe Exacerbation

Treatments: Drug: lamivudine; Drug: Tenofovir

Study type: Interventional

Funder types: Other

Identifiers

NCT01848743

Gilead IN-US-174- 0190

Details and patient eligibility

About

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.

Enrollment: 120 estimated patients

Sex: All

Ages: 20 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 2 patient groups, including a placebo group

Tenofovir

Active Comparator group

Description:

All enrolled patients are randomized to tenofovir arm who receives tenofovir 300 mg qd for 36 months

Treatment:

Drug: Tenofovir

lamivudine

Placebo Comparator group

Description:

All enrolled patients are randomized to lamivudine arm who received lamivudine 100 mg qd for 6 months, followed by tenofovir for another 30 months.

Treatment:

Drug: lamivudine