Clinical trial NCT02849132: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Hepatitis B
Liver Cirrhosis
Lead sponsor: Beijing Friendship Hospital
Sponsor class: OTHER
Collaborators: name: Peking University People's Hospital
name: Fudan University
name: Affiliated Hospital of Yanbian University
name: Shanghai Public Health Clinical Center
name: Beijing YouAn Hospital
name: Nanfang Hospital, Southern Medical University
name: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
First posted: 2016-07-29
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Fibrosis regression rate
timeFrame: year 3
measure: Cumulative incidence of liver decompensation
timeFrame: year 8
Secondary outcomes:
measure: Virological response
timeFrame: year 3, 5, 7 and 10
measure: Aminotransferase response
timeFrame: year 3, 5, 7 and 10
measure: HBeAg loss or HBeAg seroconversion
timeFrame: year 2, 5, 7 and 10
measure: HBsAg loss or HBsAg seroconversion rate
timeFrame: year 2, 5, 7 and 10
measure: Dynamic changes of Child-Pugh score
timeFrame: year 3, 5, 7 and 10
measure: Dynamic changes of MELD score
timeFrame: year 3, 5, 7 and 10
measure: Dynamic changes of liver stiffness values measured by Transient Elastography
timeFrame: year 3, 5, 7 and 10
measure: Improvement of life quality (SF36 and EQ-5D)
timeFrame: year 3, 5, 7 and 10
Other outcomes:
Locations:
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: Guangzhou
country: China
facility: NanfangHospital,Southern Medical University
state: Guangdong
city: Shijiazhuang
country: China
facility: The Third Hospital of Hebei Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: Shijiazhuang Fifth Hospital
state: Hebei
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College , Huazhong University of Science and Technology
state: Hubei
city: Yanji
country: China
facility: The Affiliated Hospital of Yanbian University
state: Jilin
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiao Tong University, School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai General 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: Xi'an
country: China
facility: Xijing Hospital, Fourth Military Medical University
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Xiqing Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
state: Zhejiang
city: Tianjin
country: China
facility: Tianjin Third Central Hospital
Study officials:
affiliation: Beijing Friendship Hospital
name: Xiaojuan Ou
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.