Clinical trial NCT01943617: Optimized Treatment and Regression of HBV-induced Compensated Liver Cirrhosis
Official title: Optimized Treatment and Regression of HBV-induced Compensated Liver Cirrhosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Liver Cirrhosis
Keywords: Liver Cirrhosis
Hepatitis B
Compensation
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: 2013-09-17
Enrollment: 606
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: 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;


Eligibility criteria: 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.

Primary outcomes:
measure: Decompensated rate of Liver Cirrhosis after 2 years treatment
timeFrame: 2 years
Secondary outcomes:
measure: Child-Pugh and MELD scores
timeFrame: 1 and 2-year
measure: The HBV DNA undetectable rate
timeFrame: 1 and 2-year
measure: Liver stiffness measurement
timeFrame: 1 and 2-year
measure: Quality of Life
timeFrame: 1 and 2-year
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: 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: Peking University People's Hospital
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 University
state: Beijing
city: Guangzhou
country: China
facility: NanfangHospital,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: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University
state: Jiangsu
city: Yanbian
country: China
facility: The Affiliated Hospital of Yanbian University
state: Jilin
city: Shanghai
country: China
facility: RenjiHospital,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
Study officials:
affiliation: Beijing Friendship Hospital
name: Hong You, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.