Optimized Treatment and Regression of HBV-induced Early Cirrhosis

Patients with chronic hepatitis B histologically confirmed of early cirrhosis S4 (similar to metavir F4, Ishak 5/6) are randomly assigned in a 1:1 ratio. One arm is entecavir alone for 2 years; the other is entecavir for the first 0.5 year, entecavir plus thymosin 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, liver ultrasonography, and Fibroscan. The second liver biopsy will be performed to evaluate regression rate of liver fibrosis 1.5 years after initial therapy.

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Drug: entecavir; Drug: Thymosin-α

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China, 100015
      • Beijing Ditan Hospital, Capital Medical University
    • Beijing, Beijing, China, 100039
      • 302 Military Hospital of China
    • Beijing, Beijing, China, 100050
      • Beijing Tiantan Hospital, Capital Medical University
    • Beijing, Beijing, China, 100069
      • Beijing Youan Hospital, Capital Medical University
    • Beijing, Beijing, China, 100871
      • Peking University
    • Beijing, Beijing, China, 100034
      • Peking University People's Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital, Southern Medical University
  • Hebei
    • Shijiazhuang, Hebei, China, 050021
      • Shijiazhuang Fifth Hospital
  • Hubei
    • Wuhan, Hubei, China, 300030
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science ＆Technology
  • Jilin
    • Yanji, Jilin, China, 133000
      • The Affiliated Hospital of Yanbian University
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital, Fudan University
    • Shanghai, Shanghai, China, 201508
      • Shanghai Public Health Clinical Center
    • Shanghai, Shanghai, China, 200080
      • Shanghai First People's Hospital
    • Shanghai, Shanghai, China, 200040
      • Zhongshan Hospital Fudan University
    • Shanghai, Shanghai, China, 200032
      • Renji Hospital, Shanghai Jiao Tong University, School of Medicine
  • Shanxi
    • Taiyuan, Shanxi, China, 030001
      • The First Hospital of Shanxi Medical University
  • Tianjin
    • Tianjin, Tianjin, China, 300162
      • The Hospital Affiliated to Logistics University of Chinese People's Armed Police Force
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients from age 18 to 65 years old;
2. Male or female;
3. Treatment-naive patients with chronic hepatitis B histologically confirmed of early cirrhosis S4 (similar to metavir F4, Ishak 5/6) who consent to undergo liver biopsy before and after treatment;
4. Patients with HBeAg-positive, HBVDNA>2×10<3>IU/ml or patients with HBeAg-negative, HBVDNA>2×10<2> IU/ml；
5. Agree to be followed up regularly;
6. Signature of written informed 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, thymosin or their components, and those considered not suitable for drugs used in this study;
3. Patients with HCV or HIV infection, 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 more than 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 or other organs;
8. Patients with any other reasons not suitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Entecavir Therapy; Entecavir monotherapy: entecavir, 0.5mg, qd, oral, for 2 years.	Drug: entecavir; anti-viral therapy; Other Names: entecavir dispersible tablets
Experimental: Entecavir plus Thymosin-α; entecavir plus Thymosin-α 1.6μg, Twice a week, ih, in the middle of 1 year.	Drug: entecavir; anti-viral therapy; Other Names: entecavir dispersible tablets; Drug: Thymosin-α; antiviral and antifibrosis therapy; Other Names: Zadaxin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regression of HBV-induced liver cirrhosis	Liver cirrhosis regression of 1 point by Ishak scoring system	1.5 to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Child-Pugh score	Child-Pugh score change after 1 and 2-year treatment	1 year and 2 years
HBVDNA undetectable rate	The HBVDNA undetectable rate after 1 and 2-year treatment.	1 year and 2 years
Fibroscan value	Fibroscan value change after 1 and 2-year treatment	1 year and 2 years
Life Quality	Life quality change after 1 and 2-year treatment by SF-36 and EQ-5D questionaire	1 year and 2 years

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Collaborators: Peking University; Peking University First Hospital; Peking University People's Hospital; Fudan University; Beijing YouAn Hospital; Beijing Ditan Hospital; Peking Union Medical College Hospital; Beijing Tiantan Hospital; Shanghai Zhongshan Hospital; Beijing 302 Hospital; RenJi Hospital; Huashan Hospital; Tongji Hospital; Nanfang Hospital of Southern Medical University; Shanghai Public Health Clinical Center; Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine; Tang-Du Hospital; Sir Run Run Shaw Hospital; The First Affiliated Hospital of Shanxi Medical University; Logistics University of Chinese People's Armed Police Forces; Fifth Hospital of Shijiazhuang City; The Affiliated Hospital of Yanbian University

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: September 5, 2013
• First Submitted That Met QC Criteria: September 5, 2013
• First Posted (Estimate): September 10, 2013

Study Record Updates

• Last Update Posted (Actual): July 27, 2018
• Last Update Submitted That Met QC Criteria: July 26, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Liver Cirrhosis; Efficacy; Hepatitis B; Regression
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Anti-Infective Agents; Antiviral Agents; Entecavir
• Other Study ID Numbers: 2013ZX10002004-2