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Effect of Entecavir Treatment on Regression and Disease Outcome in HBV-induced Liver Fibrosis and Cirrhosis Patients

Primary Purpose

Hepatitis B, Liver Cirrhosis

Status
Active
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Entecavir
Sponsored by
Beijing Friendship Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

- Subjects who completed the 2 years of entecavir-based therapy in Regress study; Subjects who are willing to participate the extension study.

Exclusion Criteria:

- Any complication of severe heart, lung, kidney, brain, blood diseases or other important systematic diseases; Pregnant women; Subjects who could not compliance with the protocol judged by investigators; Subjects who are not suitable for the study judged by investigators.

Sites / Locations

  • Peking University First Hospital
  • 302 Military Hospital Of China
  • Beijing Friendship Hospital, Capital Medical University
  • Beijing Tiantan Hospital, Capital Medical University
  • Peking University People's Hospital
  • Beijing YouAn Hospital, Capital Medical University
  • NanfangHospital,Southern Medical University
  • The Third Hospital of Hebei Medical University
  • Shijiazhuang Fifth Hospital
  • Tongji Hospital, Tongji Medical College , Huazhong University of Science and Technology
  • The Affiliated Hospital of Yanbian University
  • Renji Hospital, Shanghai Jiao Tong University, School of Medicine
  • Zhongshan Hospital Fudan University
  • Shanghai General Hospital
  • Shanghai Public Health Clinical Center
  • The First Hospital of Shanxi Medical University
  • Xijing Hospital, Fourth Military Medical University
  • Tianjin Xiqing Hospital
  • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
  • Tianjin Third Central Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment group

Arm Description

entecavir oral，0.5mg daily for 8 years

Outcomes

Primary Outcome Measures

Fibrosis regression rate
Ishak fibrosis score decrease after long-term treatment
Cumulative incidence of liver decompensation
Cumulative incidence of liver decompensation (including ascites, hepatic encephalopathy, esophageal varices bleeding and Hepatocellular Carcinoma) and death after long-term treatment

Secondary Outcome Measures

Virological response
Percentage of patients achieving hepatitis B virus (HBV) DNA < 20IU/mL at year 3, 5, 7 and 10
Aminotransferase response
The percentage of patients with alanine aminotransferase (ALT) normalization at year 3, 5, 7 and 10
HBeAg loss or HBeAg seroconversion
Percentage of patients with HBeAg loss or HBeAg seroconversion at year 2, 5, 7 and 10
HBsAg loss or HBsAg seroconversion rate
Percentage of patients with HBsAg loss or HBsAg seroconversion at year 2, 5, 7 and 10
Dynamic changes of Child-Pugh score
Dynamic changes of Child-Pugh score after 3, 5, 7 and 10 years of treatment
Dynamic changes of MELD score
Dynamic changes of MELD score after 3, 5, 7 and 10 years of treatment
Dynamic changes of liver stiffness values measured by Transient Elastography
Dynamic changes of liver stiffness values after 3, 5, 7 and 10 years of treatment
Improvement of life quality (SF36 and EQ-5D)
Improvement of life quality after 3, 5, 7 and 10 years of treatment

Full Information

First Posted
July 22, 2016
Last Updated
April 25, 2021
Sponsor
Beijing Friendship Hospital
Collaborators
Peking University People's Hospital, Fudan University, Affiliated Hospital of Yanbian University, Shanghai Public Health Clinical Center, Beijing YouAn Hospital, Nanfang Hospital, Southern Medical University, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT02849132
Brief Title
Effect of Entecavir Treatment on Regression and Disease Outcome in HBV-induced Liver Fibrosis and Cirrhosis Patients
Official Title
Effect of Entecavir Treatment on Regression and Long-term Disease Outcome in Patients With HBV-induced Liver Fibrosis and Cirrhosis (Regress Extension Study)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 2016 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beijing Friendship Hospital
Collaborators
Peking University People's Hospital, Fudan University, Affiliated Hospital of Yanbian University, Shanghai Public Health Clinical Center, Beijing YouAn Hospital, Nanfang Hospital, Southern Medical University, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

4. Oversight

5. Study Description

Brief Summary
Patients who have completed 2 years follow-up of the past National 12th Five-Year Major Project on Infectious Diseases will receive another 8 years treatment with entecavir (10 years in total). Collect serology, imaging, and other clinical data to evaluate the incidence and mortality of decompensated cirrhosis and hepatocellular carcinoma. Understand the effects of long-term antiviral therapy on HBV-induced liver fibrosis/cirrhosis.
Detailed Description
Patients who have completed 2-years entecavir-based treatment in Regress Study will receive another 8 years of entecavir extension therapy. Patients will be assessed at baseline and every six months for blood cell count, liver function test, HBV-DNA, AFP, prothrombin time, liver ultrasonography, and Fibroscan; A third liver biopsy will be performed at the 5th year of treatment in patients who have significant fibrosis at second biopsy. CT /MRI and endoscopy will be performed at baseline and the 5th and 10th year of treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Liver Cirrhosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
800 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment group
Arm Type
Experimental
Arm Description
entecavir oral，0.5mg daily for 8 years
Intervention Type
Drug
Intervention Name(s)
Entecavir
Intervention Description
oral entecavir 0.5mg daily for 8 years
Primary Outcome Measure Information:
Title
Fibrosis regression rate
Description
Ishak fibrosis score decrease after long-term treatment
Time Frame
year 3
Title
Cumulative incidence of liver decompensation
Description
Cumulative incidence of liver decompensation (including ascites, hepatic encephalopathy, esophageal varices bleeding and Hepatocellular Carcinoma) and death after long-term treatment
Time Frame
year 8
Secondary Outcome Measure Information:
Title
Virological response
Description
Percentage of patients achieving hepatitis B virus (HBV) DNA < 20IU/mL at year 3, 5, 7 and 10
Time Frame
year 3, 5, 7 and 10
Title
Aminotransferase response
Description
The percentage of patients with alanine aminotransferase (ALT) normalization at year 3, 5, 7 and 10
Time Frame
year 3, 5, 7 and 10
Title
HBeAg loss or HBeAg seroconversion
Description
Percentage of patients with HBeAg loss or HBeAg seroconversion at year 2, 5, 7 and 10
Time Frame
year 2, 5, 7 and 10
Title
HBsAg loss or HBsAg seroconversion rate
Description
Percentage of patients with HBsAg loss or HBsAg seroconversion at year 2, 5, 7 and 10
Time Frame
year 2, 5, 7 and 10
Title
Dynamic changes of Child-Pugh score
Description
Dynamic changes of Child-Pugh score after 3, 5, 7 and 10 years of treatment
Time Frame
year 3, 5, 7 and 10
Title
Dynamic changes of MELD score
Description
Dynamic changes of MELD score after 3, 5, 7 and 10 years of treatment
Time Frame
year 3, 5, 7 and 10
Title
Dynamic changes of liver stiffness values measured by Transient Elastography
Description
Dynamic changes of liver stiffness values after 3, 5, 7 and 10 years of treatment
Time Frame
year 3, 5, 7 and 10
Title
Improvement of life quality (SF36 and EQ-5D)
Description
Improvement of life quality after 3, 5, 7 and 10 years of treatment
Time Frame
year 3, 5, 7 and 10

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - Subjects who completed the 2 years of entecavir-based therapy in Regress study; Subjects who are willing to participate the extension study. Exclusion Criteria: - Any complication of severe heart, lung, kidney, brain, blood diseases or other important systematic diseases; Pregnant women; Subjects who could not compliance with the protocol judged by investigators; Subjects who are not suitable for the study judged by investigators.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaojuan Ou
Organizational Affiliation
Beijing Friendship Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking University First Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100034
Country
China
Facility Name
302 Military Hospital Of China
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100039
Country
China
Facility Name
Beijing Friendship Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100050
Country
China
Facility Name
Beijing Tiantan Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100050
Country
China
Facility Name
Peking University People's Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100050
Country
China
Facility Name
Beijing YouAn Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100069
Country
China
Facility Name
NanfangHospital,Southern Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510515
Country
China
Facility Name
The Third Hospital of Hebei Medical University
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
050051
Country
China
Facility Name
Shijiazhuang Fifth Hospital
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
50021
Country
China
Facility Name
Tongji Hospital, Tongji Medical College , Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430030
Country
China
Facility Name
The Affiliated Hospital of Yanbian University
City
Yanji
State/Province
Jilin
ZIP/Postal Code
133000
Country
China
Facility Name
Renji Hospital, Shanghai Jiao Tong University, School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Zhongshan Hospital Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200040
Country
China
Facility Name
Shanghai General Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200080
Country
China
Facility Name
Shanghai Public Health Clinical Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
201508
Country
China
Facility Name
The First Hospital of Shanxi Medical University
City
Taiyuan
State/Province
Shanxi
ZIP/Postal Code
30001
Country
China
Facility Name
Xijing Hospital, Fourth Military Medical University
City
Xi'an
State/Province
Shanxi
ZIP/Postal Code
710032
Country
China
Facility Name
Tianjin Xiqing Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300380
Country
China
Facility Name
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310016
Country
China
Facility Name
Tianjin Third Central Hospital
City
Tianjin
ZIP/Postal Code
300170
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
20558165
Citation
Arvaniti V, D'Amico G, Fede G, Manousou P, Tsochatzis E, Pleguezuelo M, Burroughs AK. Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis. Gastroenterology. 2010 Oct;139(4):1246-56, 1256.e1-5. doi: 10.1053/j.gastro.2010.06.019. Epub 2010 Jun 14.
Results Reference
background
PubMed Identifier
15470215
Citation
Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004 Oct 7;351(15):1521-31. doi: 10.1056/NEJMoa033364.
Results Reference
background
PubMed Identifier
34843068
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.
Results Reference
derived
PubMed Identifier
33460002
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.
Results Reference
derived
PubMed Identifier
32568867
Citation
Yang JM, Chen LP, Wang YJ, Lyu B, Zhao H, Shang ZY, Li J, Fan ZY, Wu SD, Ming X, Li X, Huang SP, Cheng JL. Entecavir add-on Peg-interferon therapy plays a positive role in reversing hepatic fibrosis in treatment-naive chronic hepatitis B patients: a prospective and randomized controlled trial. Chin Med J (Engl). 2020 Jul 20;133(14):1639-1648. doi: 10.1097/CM9.0000000000000857.
Results Reference
derived

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Effect of Entecavir Treatment on Regression and Disease Outcome in HBV-induced Liver Fibrosis and Cirrhosis Patients

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