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

Hepatitis B Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02849132
• Other study ID #: 2016ZX10002011
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: January 2016
• Est. completion date: December 2025

Study information

• Verified date: April 2021
• Source: Beijing Friendship Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 800
• Est. completion date: December 2025
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fibrosis
• Hepatitis B
• Liver Cirrhosis

Intervention

Drug:
• Entecavir
oral entecavir 0.5mg daily for 8 years

Locations

Country	Name	City	State
China	302 Military Hospital Of China	Beijing	Beijing
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Tiantan Hospital, Capital Medical University	Beijing	Beijing
China	Beijing YouAn Hospital, Capital Medical University	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	NanfangHospital,Southern Medical University	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	Renji Hospital, Shanghai Jiao Tong University, School of Medicine	Shanghai	Shanghai
China	Shanghai General Hospital	Shanghai	Shanghai
China	Shanghai Public Health Clinical Center	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	Shijiazhuang Fifth Hospital	Shijiazhuang	Hebei
China	The Third Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The First Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Tianjin Third Central Hospital	Tianjin
China	Tianjin Xiqing Hospital	Tianjin	Tianjin
China	Tongji Hospital, Tongji Medical College , Huazhong University of Science and Technology	Wuhan	Hubei
China	Xijing Hospital, Fourth Military Medical University	Xi'an	Shanxi
China	The Affiliated Hospital of Yanbian University	Yanji	Jilin

Sponsors (8)

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

Country where clinical trial is conducted

China, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fibrosis regression rate	Ishak fibrosis score decrease after long-term treatment	year 3
Primary	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	year 8
Secondary	Virological response	Percentage of patients achieving hepatitis B virus (HBV) DNA < 20IU/mL at year 3, 5, 7 and 10	year 3, 5, 7 and 10
Secondary	Aminotransferase response	The percentage of patients with alanine aminotransferase (ALT) normalization at year 3, 5, 7 and 10	year 3, 5, 7 and 10
Secondary	HBeAg loss or HBeAg seroconversion	Percentage of patients with HBeAg loss or HBeAg seroconversion at year 2, 5, 7 and 10	year 2, 5, 7 and 10
Secondary	HBsAg loss or HBsAg seroconversion rate	Percentage of patients with HBsAg loss or HBsAg seroconversion at year 2, 5, 7 and 10	year 2, 5, 7 and 10
Secondary	Dynamic changes of Child-Pugh score	Dynamic changes of Child-Pugh score after 3, 5, 7 and 10 years of treatment	year 3, 5, 7 and 10
Secondary	Dynamic changes of MELD score	Dynamic changes of MELD score after 3, 5, 7 and 10 years of treatment	year 3, 5, 7 and 10
Secondary	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	year 3, 5, 7 and 10
Secondary	Improvement of life quality (SF36 and EQ-5D)	Improvement of life quality after 3, 5, 7 and 10 years of treatment	year 3, 5, 7 and 10