Combination Treatment of NAs and Peg IFN α-2b for Hepatitis B Related, Compensatory Cirrhosis Patients

NCT ID: NCT03969017

Last Updated: 2019-06-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-17
• Study Completion Date: 2024-05-30

Brief Summary

The study aims to demonstrate that whether treatment of nucleoside （acid）analogues (NAs) plus pegylated interferon (Peg IFN) α-2b for those NAs treated, low level of HBsAg, hepatitis B related compensatory cirrhosis patients will result in higher HBsAg clearance rate and reduce the risk of liver cancer. The investigators plan to enroll about 84 hepatitis B related compensatory cirrhosis patients, who have received NAs treatment more than 1 year with the level of HBsAg <1000IU/ml. These participants will be devided into 2 groups. Group A will receive the treatment of NAs plus Peg IFNα-2b. Group B will be treated with NAs as before enrollment. The participants in both groups will be followed up for 96 weeks.

The primary endpoint is to compare the clearance rate of HBsAg between two groups. The secondary endpoint includes: (1) comparing the incidence of liver cancer during the 96 weeks follow-up, (2) comparing adverse side effects between the 2 groups. (3) comparing the virological and biochemical responses between the 2 groups.

Detailed Description

Clearance of hepatitis B virus surface antigen (HBsAg) is considered to be the ultimate therapeutic goal for hepatitis B patients, for it is related with low incidence of fibrosis and liver cancer. The investigators' previous study show that nucleoside （acid）analogues (NAs) treated, non-cirrhosis hepatitis B patients switched to /or combined with pegylated interferon (Peg IFN)α-2b could obtain a higher HBsAg clearance rate. Hence, the investigators' hypothesis is that treatment of NAs plus Peg IFNα-2b for those NAs treated, low level of HBsAg, hepatitis B related compensatory cirrhosis patients result in higher HBsAg clearance rate and reduce the risk of liver cancer.

The investigators plan to enroll about 84 hepatitis B related compensatory cirrhosis patients, who have received NAs treatment more than 1 year with the level of HBsAg <1000IU/ml. These participants will be devided into 2 groups according to their wishes. Group A will receive the treatment of NAs (patients previously treated with telbivudine will be changed to entecavir) plus Peg IFNα-2b （180ug per week, the dose will be changed to 135ug or 90ug per week during the treatment if patients could not tolerate the side effects of Peg IFNα-2b）. Peg IFNα-2b treatment will be performed until HBsAg <0.05IU/ml, with a maximum duration of 48 weeks. Group B will be treated with NAs as before enrollment. The participants in both groups will be followed up for 96 weeks.

The primary endpoint is to compare the clearance rate of HBsAg between two groups. The secondary endpoint includes: (1) comparing the incidence of liver cancer during the 96 weeks follow-up, (2) comparing adverse side effects, such as ascites, gastrointestinal bleeding, encephalopathy, hepatorenal syndrome between the 2 groups. (3) comparing the virological and biochemical responses between the 2 groups.

Conditions

Cirrhosis of Liver Due to Hepatitis B (Disorder)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NAs+Peg IFN Group

NAs+Peg IFN Group will receive the treatment of NAs (patients previously treated with telbivudine will be changed to entecavir) plus pegylated interferon (Peg IFN)α-2b.

Group Type: EXPERIMENTAL

pegylated interferon (Peg IFN)α-2b

Intervention Type: DRUG

Participants in NAs+Peg IFN Group will be treated by Peg IFNα-2b （180ug per week, the dose will be changed to 135ug or 90ug per week during the treatment if patients could not tolerate the side effects of Peg IFNα-2b). Peg IFNα-2b treatment will be performed until HBsAg \<0.05IU/ml, with a maximum duration of 48 weeks.

Nucleoside （acid）analogue (NAs)

Intervention Type: DRUG

Both of NAs Group and NAs+Peg IFN Group will be treated with NAs as before enrollment.

NAs Group

NAs Group will be treated with NAs as before enrollment.

Group Type: OTHER

Nucleoside （acid）analogue (NAs)

Intervention Type: DRUG

Both of NAs Group and NAs+Peg IFN Group will be treated with NAs as before enrollment.

Interventions

pegylated interferon (Peg IFN)α-2b

Participants in NAs+Peg IFN Group will be treated by Peg IFNα-2b （180ug per week, the dose will be changed to 135ug or 90ug per week during the treatment if patients could not tolerate the side effects of Peg IFNα-2b). Peg IFNα-2b treatment will be performed until HBsAg \<0.05IU/ml, with a maximum duration of 48 weeks.

Intervention Type: DRUG

Nucleoside （acid）analogue (NAs)

Both of NAs Group and NAs+Peg IFN Group will be treated with NAs as before enrollment.

Intervention Type: DRUG

Other Intervention Names

Pi Gebin; Boludine

Eligibility Criteria

Inclusion Criteria

• Aged 16-65 years old; Clinical diagnosis of compensatory cirrhosis; Child-Pugh grade A; Positive serum hepatitis B surface antigen (HBsAg); HBsAg titer < 1000IU/ml; Treated by nucleoside （acid）analogues (NAs) more than 1 year; HBV DNA <20 IU/ml; Negative serum hepatitis B e antigen (HBeAg); 15 minutes retention rate of indocyanine green <10%; The blood routine examination: 4×10e9/L<WBC<10×10e9/L、100×10e9/L<PLT<300×10e9/L.

Exclusion Criteria

• Treated by interferon within half a year; Drug induce liver diseases; Autoimmune liver diseases; Liver diseases caused by metabolic factors; Superinfection with hepatitis A, C, D, E viruses; Infected by HIV virus; Severe respiratory diseases; Severe circulatory diseases, ; Severe digestive diseases; Severe neurological diseases; Need for immunosuppressive therapy for other diseases; Need for radiotherapy/chemotherapy for other diseases; Thyroid diseases; Rheumatic diseases; Malignant tumors; Severe varicose esophageal and gastric fundus veins; Mental or psychological disorders; Alcohol or drug abusers (average alcohol consumption >40g/d for men, >20g/d for women); With contraindications to interferon therapy; Pregnancy or having pregnancy plan in 3 years; Lactation; Can not comply with the study protocol; Fail to sign the informed consent; Other conditions that are not suitable for enrollment determined by researchers.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Lin Bingliang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bingliang Lin, Doctor

Role: PRINCIPAL_INVESTIGATOR

Third Affiliated Hospital, Sun Yat-Sen University

Locations

Third Affliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Bingliang Lin, Doctor

Role: CONTACT

lamikin@126.com

86-020-85253165

Junfeng Chen, Master

Role: CONTACT

mountainchen@139.com

86-020-85253165

Facility Contacts

Lin Bingliang, MD

Role: primary

lamikin@126.com

86-20-85253165

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Other Identifiers

I-CURE VI STUDY

Identifier Type: -

Identifier Source: org_study_id