Clinical trial NCT01938781: Optimized Treatment and Regression of HBV-induced Liver Fibrosis
Official title: Optimized Treatment and Regression of HBV-induced Liver Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Liver Fibrosis
Keywords: Hepatitis B
Liver fibrosis
Regression
Efficacy
Lead sponsor: Beijing Friendship Hospital
Sponsor class: OTHER
Collaborators: name: Peking University People's Hospital
name: RenJi Hospital
name: Peking University
name: Shanghai Zhongshan Hospital
name: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
name: Shanghai Public Health Clinical Center
name: Nanfang Hospital, Southern Medical University
name: Sir Run Run Shaw Hospital
name: Beijing YouAn Hospital
name: Peking University First Hospital
name: Beijing 302 Hospital
name: Peking Union Medical College Hospital
name: Beijing Ditan Hospital
name: Beijing Tiantan Hospital
name: Huashan Hospital
name: Tongji Hospital
name: Tang-Du Hospital
name: Fifth Hospital of Shijiazhuang City
name: Logistics University of Chinese People's Armed Police Forces
name: The First Affiliated Hospital of Shanxi Medical University
name: The Affiliated Hospital of Yanbian University
First posted: 2013-09-10
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Regression Rate of HBV-induced Liver Fibrosis
timeFrame: 1.5 to 2 years
Secondary outcomes:
measure: HBVDNA undetectable rate
timeFrame: 1 year and 2 years
measure: Fibroscan scores
timeFrame: 1 year and 2 years
measure: Life Quality
timeFrame: 1 year and 2 years
measure: Incidence of drug resistance
timeFrame: 1 year and 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Ditan Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Beijing
country: China
facility: 302 Military Hospital Of China
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing YouAn Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Uiversity
state: Beijing
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Shijiazhuang
country: China
facility: Shijiazhuang Fifth Hospital
state: Hebei
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science ＆Technology
state: Hubei
city: Yanji
country: China
facility: The Affiliated Hospital of Yanbian University
state: Jilin
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiao Tong University, School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Huashan Hospital FuDan University
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai First People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
state: Shanghai
city: Taiyuan
country: China
facility: The First Hospital of Shanxi Medical University
state: Shanxi
city: Tianjin
country: China
facility: The Hospital Affiliated to Logistics University of Chinese People's Armed Police Force
state: Tianjin
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
state: Zhejiang
Study officials:
affiliation: Beijing Friendship Hospital
name: Hong You, Doctor
role: PRINCIPAL_INVESTIGATOR
References: