An Open, Multi-center Clinical Study of Combination Therapy With Tenofovir Disoproxil Fumarate and Peginterferon Alpha 2a in Nucleos(t)Ide Analogs Experienced Patients With HBV Related Hepatic Fibrosis.
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Enrollment
- 186
- Locations
- 1
- Primary Endpoint
- Ratio of regression of fibrosis
Study Overview
Brief Summary
Compared to TDF, peginterferon alfa 2a may has more therapeutic efficacy in hepatitis B surface antigen or e antigen seroconversion and anti-tumor occurrence in chronic hepatitis b patients. We design this study to compare the effectiveness and safety between the combination therapy of TDF and peg-IFN with TDF alone in NAs experienced patients with HBV related liver fibrosis. Especially the improvement of liver fibrosis and the occurrence of long-term end-stage liver disease such as cirrhosis, liver cancer, etc.
Detailed Description
Compared to TDF, peginterferon alfa 2a may has more therapeutic efficacy in hepatitis B surface antigen or e antigen seroconversion and anti-tumor occurrence in chronic hepatitis b patients. We design this study to compare the effectiveness and safety between the combination therapy of TDF and peg-IFN with TDF alone in NAs experienced patients with HBV related liver fibrosis. Especially the improvement of liver fibrosis and the occurrence of long-term end-stage liver disease such as cirrhosis, liver cancer, etc.
Main purpose: Comparing the improvement rate of liver fibrosis. Secondary purpose: Comparing the incidence of adverse events. Comparing the incidence of cirrhosis, hepatocellular carcinoma, and liver failure.
Comparing the rates of HBsAg and HBeAg serological conversion.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Positive hepatitis b surface antigen or hepatitis b virus DNA > 0.5 year;
- •Receiving treatment of nucleoside/nucleotide analogues at least one year before recruited;
- •Age from 18 to 55 years old;
- •Normal liver function(ALT<ULN,AST<ULN and TBil<ULN).
- •Undetectable hepatitis b virus DNA or less than 100IU/ml.
- •LSM between 6 and 12 kpa measured by fibroscan;
- •Liver ultrasound: normal or echo thickening, and portal vein diameter ≤ 12mm.
Exclusion Criteria
- •Decompensated cirrhosis, hepatocellular carcinoma or other malignancy;
- •Pregnancy, lactation or female has plan of pregnancy within 18 months;
- •Accompanied with other active liver diseases(HAV, HCV, HDV, HEV, autoimmune liver disease, drug-induced liver injury, alcoholic liver disease, genetic metabolic liver disease, etc.)；
- •Accompanied with human immunodeficiency virus infection or congenital immune deficiency diseases;
- •Accompanied with severe diabetes, autoimmune diseases etc. and other important organ dysfunctions;
- •Patients who fail to comply with this research arrangement and sign an informed consent form
- •Patients can not follow-up;
- •Investigator considering inappropriate.
Arms & Interventions
TDF group
93 patients would receive treatment of oral medication of tenofovir disoproxil fumarate (TDF) 300mg once per day from baseline to 48 weeks. Then they would receive oral medication of TDF 300 mg once per day from 49 to 96 weeks.
Intervention: Tenofovir Disoproxil Fumarate (Drug)
Combination group
93 patients would receive treatment of subcutaneous injection of peginterferon alfa 2a 180 μg once per week and meanwhile oral medication of tenofovir disoproxil fumarate (TDF) 300 mg once per day from baseline to 48 weeks. Then they would receive oral medication of TDF 300 mg once per day from 49 to 96 weeks.
Intervention: Tenofovir Disoproxil Fumarate (Drug)
Combination group
93 patients would receive treatment of subcutaneous injection of peginterferon alfa 2a 180 μg once per week and meanwhile oral medication of tenofovir disoproxil fumarate (TDF) 300 mg once per day from baseline to 48 weeks. Then they would receive oral medication of TDF 300 mg once per day from 49 to 96 weeks.
Intervention: PEG-Interferon alfa 2a (Drug)
Outcomes
Primary Outcomes
Ratio of regression of fibrosis
Time Frame: 48 weeks; 96 weeks
Regression of fibrosis was defined as liver stiffness measured by transient elastography changed from 9\~12kpa to 6\~9kpa or below, and from 6\~9kpa to less than 6kpa. After treatment, the proportion of patients with regression of fibrosis in the two groups was the ratio of regression of fibrosis, separately.
Secondary Outcomes
- Ratio of loss of hepatitis b e antigen or/and seroconversion(24 week, 48 week, 72 week, 96 week)
- Ratio of loss of hepatitis b s antigen or/and seroconversion(24 week, 48 week, 72 week, 96 week)
- Logarithmic mean of HBsAg decline(24 week, 48 week, 72 week, 96 week)
Investigators
Liang Peng
Professor
Third Affiliated Hospital, Sun Yat-Sen University