Combination or Sequential Therapy of Peginterferon Alfa-2a and Entecavir for Patients With Chronic Hepatitis B

Phase 4UnknownNCT01906580

Beijing 302 Hospital105 enrolled

Overview

Currently, seven medications are approved for the treatment of hepatitis B: two formulations of interferon and five nucleons(t)ide analogues. The current treatment strategy of chronic hepatitis B is now standard: initial selection of entecavir, tenofovir, or peginterferon alfa-2a (peg-IFNα-2a). Interferon is administered for a finite duration while nucleotide analogues are usually administered for many years. But among hepatitis B e antigen （HBeAg） positive patients with high serum hepatitis B virus DNA levels, the rates of virological response are poor. And antiviral drug resistance is a major limiting factor to the success of nucleotide analogue treatment. Therefore, combination therapy using peginterferon with an oral agent with a high genetic barrier to resistance might be superior to standard current monotherapy. However, the addition of lamivudine to peg-IFNα-2a therapy led to a greater decrease in serum HBV DNA levels during treatment but did not increase the rate of HBeAg sero¬conversion. Entecavir is a nucleoside analogue superior to lamivudine and adefovir in achieving higher virological response, histological improvement and normalisation of ALT. Moreover, Entecavir has a high genetic barrier with a very low incidence of drug resistance. This study is aimed to investigate the efficacy of combination or sequential therapy using peg-IFNα-2a and entecavir in HBeAg-positive chronic hepatitis B(CHB) patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

105

Conditions

Chronic Hepatitis B

Eligibility

Sex: ALLMin age: 16 YearsMax age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age≥16 years 2. HBsAg positive for more than 6 months, and HBeAg detection is positive for two times in 6 months before enrollment 3. Serum HBVDNA \>2×10\^4IU/ml 4. 80U/L \< serum ALT \< 400U/L, and TBIL \< 34 umol/L 5. Serum ALT \< 80U/L, but hepatic inflammation scores ≥ G2 or hepatic fibrosis stage ≥ S3 Exclusion Criteria: 1. Co-infected with HCV, HDV or HIV, or autoimmune liver diseases combined 2. Hepatic decompensation 3. received antiviral therapy or immunosuppressant drugs before 6 months prior to enrollment 4. Blood routine examination: WBC \<3×10\^9/L，neutrophile granulocyte \< 1.5×10\^9/L，PLT \<80×10\^9/L 5. Renal function: creatinine \>1.5 times of upper normal limit 6. Alcoholism or a history of addiction and abuse 7. Combined with hepatocarcinoma

Outcomes

Primary Outcomes

the rates of HBeAg seroconversion

Time frame: at week 72

Secondary Outcomes

normalisation of ALT

Time frame: at week 2、4、12、24、36、48、60、72、84、96

liver histological improvement

Time frame: at baseline and at week 72

The rates of HBsAg negative

Time frame: at week12、24、36、48、60、72、84、96

the rate of virological response

Time frame: at week 4、12、24、36、48、60、72、84、96

the rate of HBeAg negative

Time frame: at week 12、24、36、48、60、72、84、96