Clinical trial NCT02945982: Treatment of Moderate and Severe Cirrhotic Portal Hypertension Due to HBV With Fuzheng Huayu and Entecavir
Official title: A Randomized, Placebo-Controlled, Open-label, Multi-Center Study to Assess the Efficacy and Safety of Fuzheng Huayu Combined With Entecavir and Carvedilol in Moderate and Severe Cirrhotic Portal Hypertension Due to Hepatitis B Virus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Portal Hypertension
Keywords: Portal Hypertension
Fuzheng Huayu
Hepatitis B
Lead sponsor: ShuGuang Hospital
Sponsor class: OTHER
Collaborators: name: Ruijin Hospital
name: Shanghai Zhongshan Hospital
name: Longhua Hospital
name: Shanghai Public Health Clinical Center
First posted: 2016-10-26
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Portal hypertension is a common pathology in chronic liver disease, particularly in liver cirrhosis. Hepatitis B Virus (HBV) is one of most etiologies of liver cirrhosis in China. The basic reason for portal hypertension in HBV is the largely deposition of hepatic extracellular matrixes which causes high pressure in liver vessels. One of the most common symptoms of cirrhotic portal hypertension is gastroesophageal varices.The effective inhibition of HBV can partially stop or reverse liver fibrosis in patients with chronic Hepatitis and liver cirrhosis due to HBV and the anti-fibrotic strategy focusing on the regulation of hepatic extracellular matrix may have a great benefit. Therefore, antivirals therapy is also a basic treatment for low-grade cirrhotic portal hypertension. 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 relieve the pressure of liver vessels and decline incidence rate and bleeding rate of gastroesophageal varices.

Detailed description: The primary objective of this study is to establish the safety and efficacy of the combination of Entecavir and Fuzheng Huayu for reverse rate of gastroesophageal varices in patients with Moderate and Severe cirrhotic portal hypertension due to hepatitis B virus.

Eligibility criteria: Inclusion Criteria:

* More than 6 months history of serum positive HBsAg
* Abdominal ultrasonogram or CT scan or liver-biopsy specimen indicates liver cirrhosis
* Age 18-65
* Child-Pugh\<7 (Stage A)
* Without portal hypertension（Endoscopy indicates no signs of gastroesophageal varices.）
* Moderate and Severe of portal hypertension（Endoscopy indicates signs of gastroesophageal varices that is line shape without red wales or spots and less than 0.3cm of diameter.）
* The patient or the patient's guardian agrees to participate the random controlled trial and sign the Informed Consent Form.

Exclusion Criteria:

* Primary Lamivudine, Adefovir dipivoxil and Entecavir resistance
* Decompensated cirrhosis、The Child-Pugh score≥7
* Low-grade Cirrhotic Portal Hypertension.
* Severe grade of portal hypertension（Endoscopy indicates signs of gastroesophageal varices that is catenulate/nodular shape with or without red wales or spots and more than 1.0cm of diameter.）
* Decompensated liver cirrhosis Liver cancer
* 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 anti-viral or anti-fibrosis drug within 6 months.
* Patients who are participating other trials.
* Other situation where PI thinks the patient should be excluded.

Primary outcomes:
measure: Incidence of clinical events: Variceal hemorrhage, Ascites, Encephalopathy, etc
timeFrame: 96 weeks
measure: Grading varices
timeFrame: 96 weeks
measure: Incidence of liver cancer
timeFrame: 96 weeks
measure: Noninvasive portal hypertension index
timeFrame: 96 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital
city: Shanghai
country: China
facility: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
Study officials:
affiliation: ShuGuang Hospital
name: CHENGHAI LIU, PHD,MD
role: PRINCIPAL_INVESTIGATOR
References: