Optimized Treatment and Regression of HBV-induced Liver Fibrosis

Phase 4

Completed

• Conditions: Liver Fibrosis
• Interventions: Drug: entecavir; Drug: Peg-IFN

• Registration Number: NCT01938781
• Lead Sponsor: Beijing Friendship Hospital

Brief Summary

Patients with chronic hepatitis B histologically confirmed of liver fibrosis S2/S3 (similar to metavir F2/F3, Ishak 2/3/4) are randomly assigned in a 1:1 ratio. One arm is entecavir alone for 2 years; the other is entecavir alone for the first 0.5 year, entecavir plus pegylated interferon (peg-IFN) for 1 year, entecavir for another additional 0.5 year. Patients will be assessed at baseline, at every six months for blood count, liver function test, HBVDNA, AFP, prothrombin time, thyroid function, liver ultrasonography, and Fibroscan. The second liver biopsy will be performed to evaluate regression rate of liver fibrosis 1.5 years after initial therapy.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06
• Study First Submitted: 2013-09-05
• Study First Submitted QC: 2013-09-05
• Study First Posted: 2013-09-10
• Primary Completion: 2016-12
• Study Completion: 2016-12
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-26
• Last Update Posted: 2018-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

1. Ages from 18 to 65 years old;
2. Male or female;
3. Treatment-naive patients with chronic HBV-induced fibrosis S2/S3 (similar to F2/F3, Ishak 2/3/4), who consent to undergo liver biopsy before and after treatment;
4. Patients with HBeAg-positive, HBVDNA>2×10<4> IU/ml or with HBeAg-negative, HBVDNA>2×10<3> IU/ml;
5. Agree to be follow-up regularly;
6. signature of written inform consent.

Exclusion Criteria

1. Patients with decompensated cirrhosis: including ascites, hepatic encephalopathy, esophageal varices bleeding or other complications of decompensated cirrhosis or hepatocelluar carcinoma;
2. Patients who are allergic to entecavir, interferon, or their components, and those considered not suitable for medications used in this study;
3. Patients coinfection with HCV or HIV, alcoholic liver disease, autoimmune liver disease, genetic liver disease, drug-induced liver injury, severe non-alcoholic fatty liver disease or other chronic liver diseases;
4. Patients with baseline AFP level higher than 100 ng/ml and possible malignant lesion on image, or AFP level higher than 100 ng/ml for continuous three months;
5. Creatinine >1.5×ULN;
6. Patients with other uncured malignant tumors;
7. Patients with severe diseases of heart, lung, kidney, brain, blood system or other organs;
8. Patients with severe neurological or psychological disease (e.g. epilepsy, depression, mania and schizophrenia);
9. Patients with poorly controlled diabetes, hypertension or thyroid disease;
10. Patients with any other reasons not suitable for the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Entecavir plus peg-IFN Therapy	entecavir	entecavir combined peg-IFN in the middle 1 year.
Entecavir plus peg-IFN Therapy	Peg-IFN	entecavir combined peg-IFN in the middle 1 year.
Entecavir monotherapy	entecavir	entecavir, 0.5mg, qd, oral, for 2 years.

Primary Outcome Measures

Name	Time	Method
Regression Rate of HBV-induced Liver Fibrosis	1.5 to 2 years	Fibrosis regression of 1 point by Ishak scoring system

Secondary Outcome Measures

Name	Time	Method
Life Quality	1 year and 2 years	Life quality after 1 and 2-year treatment by SF-36 and EQ-5D questionaire
Fibroscan scores	1 year and 2 years	Fibroscan scores after 1 and 2-year treatment
HBVDNA undetectable rate	1 year and 2 years	The HBVDNA undetectable rate after 1 year and 2-year treatment
Incidence of drug resistance	1 year and 2 years	Incidence of drug resistance after 1 and 2-year treatment

Trial Locations

Locations (21)

Beijing Ditan Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Peking University People's Hospital; 🇨🇳 Beijing, Beijing, China

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China

302 Military Hospital Of China; 🇨🇳 Beijing, Beijing, China

Beijing Tiantan Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Beijing Friendship Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China

Beijing YouAn Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Peking Uiversity; 🇨🇳 Beijing, Beijing, China

Shijiazhuang Fifth Hospital; 🇨🇳 Shijiazhuang, Hebei, China

Tongji Hospital, Tongji Medical College, Huazhong University of Science ＆Technology; 🇨🇳 Wuhan, Hubei, China

Renji Hospital, Shanghai Jiao Tong University, School of Medicine; 🇨🇳 Shanghai, Shanghai, China

The Affiliated Hospital of Yanbian University; 🇨🇳 Yanji, Jilin, China

Huashan Hospital FuDan University; 🇨🇳 Shanghai, Shanghai, China

Shanghai First People's Hospital; 🇨🇳 Shanghai, Shanghai, China

Zhongshan Hospital Fudan University; 🇨🇳 Shanghai, Shanghai, China

Shanghai Public Health Clinical Center; 🇨🇳 Shanghai, Shanghai, China

The Hospital Affiliated to Logistics University of Chinese People's Armed Police Force; 🇨🇳 Tianjin, Tianjin, China

The First Hospital of Shanxi Medical University; 🇨🇳 Taiyuan, Shanxi, China

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China

Peking University First Hospital; 🇨🇳 Beijing, Beijing, China