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

• Sponsor: Beijing Friendship Hospital (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02849132
• Collaborator: Peking University People's Hospital (Other), Fudan University (Other), Affiliated Hospital of Yanbian University (Other), Shanghai Public Health Clinical Center (Other), Beijing YouAn Hospital (Other), Nanfang Hospital of Southern Medical University (Other), Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (Other)
• Enrollment: 800
• Locations: 20
• Arm: 1
• Anticipated Duration (Months): 119
• Patients Per Site: 40
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B; Liver Cirrhosis	Drug: Entecavir	Phase 4

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 800 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Jan 1, 2016
• Anticipated Primary Completion Date: Dec 1, 2023
• Anticipated Study Completion Date: Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment group entecavir oral，0.5mg daily for 8 years	Drug: Entecavir; oral entecavir 0.5mg daily for 8 years

Outcome Measures

Primary Outcome Measures

1. Fibrosis regression rate [year 3]

   Ishak fibrosis score decrease after long-term treatment

2. Cumulative incidence of liver decompensation [year 8]

   Cumulative incidence of liver decompensation (including ascites, hepatic encephalopathy, esophageal varices bleeding and Hepatocellular Carcinoma) and death after long-term treatment

Secondary Outcome Measures

1. Virological response [year 3, 5, 7 and 10]

   Percentage of patients achieving hepatitis B virus (HBV) DNA < 20IU/mL at year 3, 5, 7 and 10

2. Aminotransferase response [year 3, 5, 7 and 10]

   The percentage of patients with alanine aminotransferase (ALT) normalization at year 3, 5, 7 and 10

3. HBeAg loss or HBeAg seroconversion [year 2, 5, 7 and 10]

   Percentage of patients with HBeAg loss or HBeAg seroconversion at year 2, 5, 7 and 10

4. HBsAg loss or HBsAg seroconversion rate [year 2, 5, 7 and 10]

   Percentage of patients with HBsAg loss or HBsAg seroconversion at year 2, 5, 7 and 10

5. Dynamic changes of Child-Pugh score [year 3, 5, 7 and 10]

   Dynamic changes of Child-Pugh score after 3, 5, 7 and 10 years of treatment

6. Dynamic changes of MELD score [year 3, 5, 7 and 10]

   Dynamic changes of MELD score after 3, 5, 7 and 10 years of treatment

7. Dynamic changes of liver stiffness values measured by Transient Elastography [year 3, 5, 7 and 10]

   Dynamic changes of liver stiffness values after 3, 5, 7 and 10 years of treatment

8. Improvement of life quality (SF36 and EQ-5D) [year 3, 5, 7 and 10]

   Improvement of life quality after 3, 5, 7 and 10 years of treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking University First Hospital	Beijing	Beijing	China	100034
2	302 Military Hospital Of China	Beijing	Beijing	China	100039
3	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing	China	100050
4	Beijing Tiantan Hospital, Capital Medical University	Beijing	Beijing	China	100050
5	Peking University People's Hospital	Beijing	Beijing	China	100050
6	Beijing YouAn Hospital, Capital Medical University	Beijing	Beijing	China	100069
7	NanfangHospital,Southern Medical University	Guangzhou	Guangdong	China	510515
8	The Third Hospital of Hebei Medical University	Shijiazhuang	Hebei	China	050051
9	Shijiazhuang Fifth Hospital	Shijiazhuang	Hebei	China	50021
10	Tongji Hospital, Tongji Medical College , Huazhong University of Science and Technology	Wuhan	Hubei	China	430030
11	The Affiliated Hospital of Yanbian University	Yanji	Jilin	China	133000
12	Renji Hospital, Shanghai Jiao Tong University, School of Medicine	Shanghai	Shanghai	China	200032
13	Zhongshan Hospital Fudan University	Shanghai	Shanghai	China	200040
14	Shanghai General Hospital	Shanghai	Shanghai	China	200080
15	Shanghai Public Health Clinical Center	Shanghai	Shanghai	China	201508
16	The First Hospital of Shanxi Medical University	Taiyuan	Shanxi	China	30001
17	Xijing Hospital, Fourth Military Medical University	Xi'an	Shanxi	China	710032
18	Tianjin Xiqing Hospital	Tianjin	Tianjin	China	300380
19	Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University	Hangzhou	Zhejiang	China	310016
20	Tianjin Third Central Hospital	Tianjin		China	300170

Sponsors and Collaborators

• Beijing Friendship Hospital
• Peking University People's Hospital
• Fudan University
• Affiliated Hospital of Yanbian University
• Shanghai Public Health Clinical Center
• Beijing YouAn Hospital
• Nanfang Hospital of Southern Medical University
• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Investigators

• Principal Investigator: Xiaojuan Ou, Beijing Friendship Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.

• Responsible Party: Xiaojuan Ou, Vice-Director of Liver Research Center, Beijing Friendship Hospital
• ClinicalTrials.gov Identifier: NCT02849132
• Other Study ID Numbers: 2016ZX10002011
• First Posted: Jul 29, 2016
• Last Update Posted: Apr 28, 2021
• Last Verified: Apr 1, 2021

• Additional relevant MeSH terms: Hepatitis B; Liver Cirrhosis; Fibrosis; Entecavir

Study Results

No Results Posted as of Apr 28, 2021