Clinical trial NCT02241616: Traditional Chinese Medicine Combined With Entecavir to Treat Refractory Liver Fibrosis in Liver Cirrhosis Due to HBV
Official title: A Multi-Center Study to Assess the Efficacy and Safety of Traditional Chinese Medicine Combined With Entecavir for Patients With Refractory Liver Fibrosis in Liver Cirrhosis Due to HBV
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hepatitis B Virus Related Cirrhosis
Lead sponsor: ShuGuang Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Zhongshan Hospital
name: Guangxi Ruikang Hospital
name: Hubei Hospital of Traditional Chinese Medicine
name: The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine
name: Huai'an No. 4 People's Hospital
name: Ruijin Hospital
name: Shenzhen Third People's Hospital
name: Beijing Ditan Hospital
name: Beijing YouAn Hospital
name: China-Japan Friendship Hospital
name: Tongji Hospital
name: Wenzhou Central Hospital
name: Jingmen No.1 People's Hospital
name: Shandong University of Traditional Chinese Medicine
name: The Ninth Hospital of Nanchang
name: The People's Hospital of Ningxia
name: Fifth Hospital of Shijiazhuang City
name: The Fifth People's Hospital of Suzhou
name: The Fifth People's Hospital of Anyang
First posted: 2014-09-16
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Liver Cirrhosis is a common pathological consequence of chronic liver disease. Hepatitis B Virus (HBV) is one of most etiologies of Liver cirrhosis in China. The effective inhibition of HBV can partially regress or reverse liver fibrosis in patients with chronic Hepatitis and liver cirrhosis due to HBV, however some patients keep existence or development although HBV DNA is under-detectable after anti-virals. Theses refractory liver fibrosis is required the anti-fibrotic treatment focusing on the regulation of hepatic extracellular matrix, especially is necessary for in the patients with advance fibrosis stage ie. liver cirrhosis. Fuzheng Huayu has been found to enhance the degradation of collagens in fibrotic liver and have a good action against liver fibrosis in patients with chronic hepatitis B. However, there are no high quality clinical evidences which can demonstrate if the combination of anti-viral and anti-fibrotic therapy can improve the reversion of refractory liver fibrosis in liver cirrhosis due to HBV.

The primary objective of this study is to establish the safety and efficacy of the combination of Entecavir and Traditional Chinese Medicine in refractory liver fibrosis in liver cirrhosis due to HBV.


Eligibility criteria: Inclusion Criteria:

* Hepatitis B history or more than 6 months history of positive HBsAg
* Within 2 years of Entecavir treatment, HBV-DNA is negative but has not reach the clinical endpoint (HBeAg seroconversion or HBsAg loss in HBeAg-positive patients; HBsAg loss or anti-HBs seroconversion in HBeAg-negative patients)
* Age 18-60
* Ishak fibrosis score of the biopsy within 6 months ≥5, no anti-fibrosis drug was taken within 6 months.
* Child-Pugh\<7 (Stage A)
* The patient or the patient's guardian agrees to participate the random controlled trial and sign the Informed Consent Form.

Exclusion Criteria:

* Decompensated liver cirrhosis
* HCC
* Liver histology conforming to other chronic liver diseases, such as moderate or severe non-alcoholic fatty liver disease(more than 1/3 steatosis in liver ), chronic hepatitis C, chronic hepatitis D, autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, inherited metabolic liver disease, drug or toxic induced liver injury, parasitic infections, alcoholic liver disease.
* Have psychiatric history or uncontrollable epilepsy patient.
* Uncontrollable diabetic patient
* History of hemoglobin disease (such as alpha- or beta-thalassemia, sickle cell disease, spherocytosis) or patients with toxic or autoimmune hemolytic anemia.
* Severe background disease like chronic respiratory failure, circulatory failure, kidney failure etc.
* In situ organ transplantation (such as liver, kidney, lung and heart) or bone marrow transplantation and stem cell transplantation.
* Immunocompromised patients: such as HIV infection or take immunosuppressor or Glucocorticoid (such as cyclosporin, azathioprine, adrenocortical hormone) within 3 months or chemotherapy drugs (such as cyclophosphamide, ammonia and cancer chemotherapy) and radioactive therapy.
* Gestation or lactation period women and women who plan to get pregnant during the study period.
* Patient who are allergy to the experimental drug.
* Using history of other anti-viral drug within 6 months.
* Patients who are participating other trials.
* Other situation where PI thinks the patient should be excluded.

Primary outcomes:
measure: Degree of liver fibrosis
timeFrame: 48 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Nanning
country: China
facility: Guangxi Ruikang Hospital
state: Guangxi
city: Shijiazhuang
country: China
facility: The Fifth Hospital of Shijiazhuang
state: Hebei
city: Anyang
country: China
facility: The Fifth People's Hospital of Anyang
state: Henan
city: Jingmen
country: China
facility: Jingmen No.1 People's Hospital
state: Hubei
city: Wuhan
country: China
facility: Hubei Hospital of TCM
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
city: Changsha
country: China
facility: The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine
state: Hunan
city: Huai'an
country: China
facility: Huai'an No. 4 People's Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The Fifth People's Hospital of Suzhou
state: Jiangsu
city: Nanchang
country: China
facility: The Ninth Hospital of Nanchang
state: Jiangxi
city: Yinchuan
country: China
facility: Ningxia People's Hospital
state: Ningxia
city: Jinan
country: China
facility: Affiliated Hospital of Shandong Univercity of TCM
state: Shandong
city: Wenzhou
country: China
facility: Wenzhou Central Hospital
state: Zhejiang
city: Beijing
country: China
facility: Beijing Ditan Hospital Capital Medical University
city: Beijing
country: China
facility: Beijing Youan Hospital Capital Medical University
city: Beijing
country: China
facility: China-Japan Friendship Hospital
city: Shanghai
country: China
facility: ShuGuang Hospital
city: Shanghai
country: China
facility: Ruijin Hospital
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital
city: Shenzhen
country: China
facility: Shenzhen Third People's Hospital
Study officials:
affiliation: ShuGuang Hospital
name: Chenghai Liu, PhD
role: STUDY_DIRECTOR
References:
citation: Chen Y, Zhao Z, Fan H, Li Z, He Y, Liu C. Safety and therapeutic effects of anti-fibrotic Traditional Chinese Medicine Fuzheng Huayu on persistent advanced stage fibrosis following 2 years entecavir treatment: Study protocol for a single arm clinical objective performance criteria trial. Contemp Clin Trials Commun. 2020 Jun 23;19:100601. doi: 10.1016/j.conctc.2020.100601. eCollection 2020 Sep.