Optimized Treatment and Regression of HBV-induced Compensated Liver Cirrhosis

Six hundreds patients with chronic hepatitis B clinically diagnosed as compensated liver cirrhosis 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 thymosin-α for 1 year, entecavir for another additional 0.5 year.Patients will be assessed at baseline, at every six months for blood cell count, liver function test, HBVDNA, AFP, prothrombin time, liver ultrasonography, and Fibroscan;

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 606
• 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, 100050
      • Peking University People's Hospital
    • Beijing, Beijing, China, 100069
      • Beijing Youan Hospital, Capital Medical University
    • Beijing, Beijing, China, 100871
      • Peking University
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • NanfangHospital,Southern Medical University
  • Hebei
    • Shijiazhuang, Hebei, China, 50021
      • Shijiazhuang Fifth Hospital
  • Hubei
    • Wuhan, Hubei, China, 300030
      • Tongji Hospital, Tongji Medical College ,Huazhong University of Science ＆Technology
  • Jiangsu
    • Hangzhou, Jiangsu, China, 310016
      • Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University
  • Jilin
    • Yanbian, 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, 200032
      • RenjiHospital,Shanghai Jiao Tong University,School of Medicine
    • Shanghai, Shanghai, China, 200040
      • Zhongshan Hospital Fudan University
  • Shanxi
    • Taiyuan, Shanxi, China, 30001
      • 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

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 ;
2. Male or female;

3. Treatment-naive patients of clinically diagnosed as HBV-induced compensated cirrhosis(meet one of the following two criterions);

   1. endoscopy: esophageal varices , exclusion of noncirrhotic portal hypertension

   2. if no endoscopy,should meet two of the four Criterias:

      • Imaging (US, CT or MRI, et al) showing Surface nodularity: Echogenecity
      • Platelet (PLT) < 100×10 < 9 >/L , no other interpretation
      • Albumin (ALB) < 35.0 g/L, or International Standard Value (INR) > 1.3 (Prothrombin Time (PT) prolonged > 3s), or Cholinesterase (CHE) decrease
      • Liver stiffness measurement value > 12.4 kpa (ALT<5×ULN)
4. HBeAg-positive, HBVDNA > 2×10<3> IU/ml or with HBeAg-negative patients, HBVDNA > 2×10<2> IU/ml;
5. Agree to be followed 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, thymosin or their components, and those considered not suitable for medicine 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 100ng/ml and possible malignant lesion on image, or AFP level higher than 100ng/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 system 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, 0.5mg, qd, oral, for 2 years	Drug: Entecavir; anti-viral therapy; Other Names: Entecavir dispersible tablets
Experimental: Entecavir plus thymosin therapy; Entecavir plus thymosin-α 1.6μg, Twice a week, ih, in the middle one year	Drug: Entecavir; anti-viral therapy; Other Names: Entecavir dispersible tablets; Drug: Thymosin-α; anti-viral and antitherapy; Other Names: Zadaxin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decompensated rate of Liver Cirrhosis after 2 years treatment	Decompensated rate of Liver Cirrhosis (ascites, hepatic encephalopathy, esophageal varices bleeding and Hepatocellular Carcinoma) after 2 years treatment.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Child-Pugh and MELD scores	The progress of Child-Pugh and MELD scores after 1 and 2-year treatment	1 and 2-year
The HBV DNA undetectable rate	The HBV DNA undetectable rate after 1 and 2-year treatment	1 and 2-year
Liver stiffness measurement	Liver stiffness measurement change after 1 and 2-year treatment.	1 and 2-year
Quality of Life	Quality of life after 1 and 2-year treatment by SF-36 and EQ-5D questionares	1 and 2-year

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Collaborators: Peking University; Peking University First Hospital; Peking University People's Hospital; 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

Publications and helpful links

General Publications

• Wu X, Zhou J, Sun Y, Ding H, Chen G, Xie W, Piao H, Xu X, Jiang W, Ma H, Ma A, Chen Y, Xu M, Cheng J, Xu Y, Meng T, Wang B, Chen S, Shi Y, Kong Y, Ou X, You H, Jia J. Prediction of liver-related events in patients with compensated HBV-induced cirrhosis receiving antiviral therapy. Hepatol Int. 2021 Feb;15(1):82-92. doi: 10.1007/s12072-020-10114-1. Epub 2021 Jan 18.
• Wu X, Hong J, Zhou J, Sun Y, Li L, Xie W, Piao H, Xu X, Jiang W, Feng B, Chen Y, Xu M, Cheng J, Meng T, Wang B, Chen S, Kong Y, Ou X, You H, Jia J. Health-related quality of life improves after entecavir treatment in patients with compensated HBV cirrhosis. Hepatol Int. 2021 Dec;15(6):1318-1327. doi: 10.1007/s12072-021-10240-4. Epub 2021 Nov 29.

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 12, 2013
• First Posted (Estimate): September 17, 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; Compensation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Anti-Infective Agents; Antiviral Agents; Entecavir
• Other Study ID Numbers: 2013ZX10002004-3