Clinical trial NCT03957629: Optimized Treatment of Peginterferon Alfa 2a in Treatment Experienced Patients With HBV Related Liver Fibrosis
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hepatitis B
Liver Fibrosis
Keywords: hepatitis b virus
liver fibrosis
peg interferon alfa-2a
tenofovir disoproxil fumarate
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2019-05-21
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Positive hepatitis b surface antigen or hepatitis b virus DNA \> 0.5 year;
2. Receiving treatment of nucleoside/nucleotide analogues at least one year before recruited;
3. Age from 18 to 55 years old;
4. Normal liver function(ALT\<ULN,AST\<ULN and TBil\<ULN).
5. Undetectable hepatitis b virus DNA or less than 100IU/ml.
6. LSM between 6 and 12 kpa measured by fibroscan;
7. Liver ultrasound: normal or echo thickening, and portal vein diameter ≤ 12mm.

Exclusion Criteria:

1. Decompensated cirrhosis, hepatocellular carcinoma or other malignancy;
2. Pregnancy, lactation or female has plan of pregnancy within 18 months;
3. 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.)；
4. Accompanied with human immunodeficiency virus infection or congenital immune deficiency diseases;
5. Accompanied with severe diabetes, autoimmune diseases etc. and other important organ dysfunctions;
6. Patients who fail to comply with this research arrangement and sign an informed consent form
7. Patients can not follow-up;
8. Investigator considering inappropriate.

Primary outcomes:
measure: Ratio of regression of fibrosis
timeFrame: 48 weeks; 96 weeks
Secondary outcomes:
measure: Ratio of loss of hepatitis b e antigen or/and seroconversion
timeFrame: 24 week, 48 week, 72 week, 96 week
measure: Ratio of loss of hepatitis b s antigen or/and seroconversion
timeFrame: 24 week, 48 week, 72 week, 96 week
measure: Logarithmic mean of HBsAg decline
timeFrame: 24 week, 48 week, 72 week, 96 week
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Third Affiliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
name: Peng, ph.D.
role: STUDY_DIRECTOR
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
name: Xu, ph.D.
role: STUDY_DIRECTOR
References: