Clinical trial NCT01848743: Tenofovir Versus Lamivudine for Patients of Chronic Hepatitis B With Severe Acute Exacerbation
Official title: Tenofovir Versus Lamivudine for Patients of Chronic Hepatitis B With Severe Acute Exacerbation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Chronic HBV With Severe Exacerbation
Keywords: tenofovir, lamivudine, hepatitis B, acute exacerbation
Lead sponsor: Kaohsiung Veterans General Hospital.
Sponsor class: OTHER
First posted: 2013-05-07
Enrollment: 120
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 6 months survival
timeFrame: 6 months after treatment begins
Secondary outcomes:
measure: rapid virological response
timeFrame: 1,2 and 4 weeks after treatment
measure: HBeAg seroconversion and virological response 1, 2, and 3 years after treatment
timeFrame: 1,2 and 3 years after treatment
measure: Safety profile
timeFrame: during and 6 months after treatment
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospigal
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
Study officials:
References:
citation: Lu CM, Cheng JS, Sun WC, Chen WC, Tsay FW, Wang HM, Tsai TJ, Kao SS, Li YD, Li YR, Lin HS, Yin CH, Tsai WL. Randomized Controlled Study of Tenofovir versus Lamivudine Followed by Tenofovir in Severe Exacerbation of Hepatitis B. Antimicrob Agents Chemother. 2022 Feb 15;66(2):e0166421. doi: 10.1128/AAC.01664-21. Epub 2021 Nov 22.