CABER: Endoscopic and Microbiological Assessment of the Effect of Carvedilol Combined With Berberine on GOV in Cirrhosis

Sponsor

Tianjin Second People's Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04543643

Collaborator

(none)

288

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Carvedilol has been shown to be more potent in decreasing portal hypertension to propranolol. A lot of studies have shown that the imbalance of flora and the progress of portal hypertension are mutually causal. Berberine can regulate the intestinal flora.In this study, we evaluated the effect of carvedilol and berberine on reducing portal vein pressure by observing the changes of endoscopy，endoscopic ultrasonography and intestinal flora.

Condition or Disease	Intervention/Treatment	Phase
Cirrhosis Due to Hepatitis B Cirrhosis Due to Hepatitis C Gastroesophageal Varices	Drug: Carvedilol Drug: Berberine	Phase 3

Detailed Description

There is a higher risk of esophageal and gastric varices bleeding in cirrhosis patients with moderate and severe esophageal and gastric varices. Once there is a high mortality rate of esophageal and gastric varices bleeding, it will cause great losses to the family and society. Therefore, it is of great social and economic significance to prevent esophageal and gastric varices bleeding through economic and effective methods. As the third generation of NSBB, carvedilol is more effective in reducing HVPG than propranolol, which is recommended by Baveno VI as the first-line drug for EVB primary prevention. A lot of studies have shown that the imbalance of flora and the progress of portal hypertension are mutually causal. The application of carvedilol can reduce the pressure of portal vein, and when the portal hypertension is improved, the imbalance of intestinal mucosal barrier and flora will also be changed. Berberine can regulate the intestinal flora, which is safe and effective in clinical application. Gastroscopy is still the main method of screening varicose veins. We can determine whether there is GOV in patients and evaluate the risk of varicose vein bleeding. However, gastroscopy can only observe the situation in the digestive tract lumen, and ultrasound endoscopy can scan the outside of the tube wall, so as to more comprehensively evaluate the change of portal hypertension. The purpose of this study is to apply endoscopic ultrasonography to the whole process of the study, which can be used as a more sensitive means to observe the changes of portal hypertension, and to systematically evaluate the continuous changes of portal hypertension. It provides a theoretical basis and measurement means for a more comprehensive and scientific evaluation of portal hypertension.In this study, the patients with GOV who need primary prevention were randomly divided into two groups. Carvedilol or carvedilol combined with berberine were given for 12 months respectively. The degree of varicose vein relief was judged by ES and EUS, and the changes of oral and intestinal flora were detected at the same time To understand the possible mechanism of carvedilol and berberine in reducing portal hypertension.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

288 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel AssignmentParallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Endoscopic and Microbiological Assessment of the Effect of Carvedilol Combined With Berberine on GOV in Cirrhosis: a Prospective Cohort Study

Anticipated Study Start Date :

Nov 1, 2021

Anticipated Primary Completion Date :

Oct 31, 2023

Anticipated Study Completion Date :

Oct 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Carvedilol+ berberine Carvedilol is started at a dose of 6.25 mg once per day. After 1 week, this will increased to a dose of 6.25 mg twice daily per day if systolic blood pressure does not fall below 85mm Hg and HR 55/min. Berberine is started at a dose of 0.3g twice per day.	Drug: Carvedilol As the third generation of NSBB, carvedilol is more effective in reducing HVPG than propranolol, which is recommended by Baveno VI as the first-line drug for EVB primary prevention. Drug: Berberine Berberine can regulate the intestinal flora, which is safe and effective in clinical application.
Active Comparator: Carvedilol Carvedilol is started at a dose of 6.25 mg once per day. After 1 week, this will increased to a dose of 6.25 mg twice daily per day if systolic blood pressure does not fall below 85 mm Hg and HR 55/min.	Drug: Carvedilol As the third generation of NSBB, carvedilol is more effective in reducing HVPG than propranolol, which is recommended by Baveno VI as the first-line drug for EVB primary prevention.

Arm

Intervention/Treatment

Experimental: Carvedilol+ berberine

Carvedilol is started at a dose of 6.25 mg once per day. After 1 week, this will increased to a dose of 6.25 mg twice daily per day if systolic blood pressure does not fall below 85mm Hg and HR 55/min. Berberine is started at a dose of 0.3g twice per day.

Drug: Carvedilol

As the third generation of NSBB, carvedilol is more effective in reducing HVPG than propranolol, which is recommended by Baveno VI as the first-line drug for EVB primary prevention.

Drug: Berberine

Berberine can regulate the intestinal flora, which is safe and effective in clinical application.

Active Comparator: Carvedilol

Drug: Carvedilol

As the third generation of NSBB, carvedilol is more effective in reducing HVPG than propranolol, which is recommended by Baveno VI as the first-line drug for EVB primary prevention.

Outcome Measures

Primary Outcome Measures

The progression Incidence of esophageal varices [1 year]
progression of esophagogastric varices under gastroscopy and/or endoscopic ultrasound

Secondary Outcome Measures

The incidence of liver cirrhosis decompensation [1 year]
the occurrence of decompensating events in cirrhosis (decompensating is defined as gastrointestinal bleeding, ascites, or significant hepatic encephalopathy, hepatorenal syndrome, associated with portal hypertension)
HCC, death or liver transplantation [1 year]
The incidence of hepatic cellular carcinoma, death or liver transplantation

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

HBV-related or/and HCV-related liver cirrhotic patients based on pathology or clinical diagnosis;
Antiviral therapy;
Male or Female;
ES showed the presence of esophageal and gastric varices and / or red signs;
Child-Pugh < 10, and meld < 29;
Signature of informed consent.

Exclusion Criteria:

• Used antibiotics, prebiotics, probiotics and proton pump inhibitors within 2 weeks;
Any contra-indications to beta-blockers including asthma, chronic obstructive pulmonary disease, allergic rhinitis, NYHA (New York Heart Association) class IV heart failure, atrioventricular block, sinus bradycardia (HR < 50 / min), cardiogenic shock, hypotension (SBP < 85mmHg), sick sinus syndrome, insulin dependent diabetes, peripheral vascular disease;
Unstable high blood pressure and long-term engagement in driving;
Any malignancy that affects survival, excluding the cured;
Patients with portal thrombosis;
PT extension greater than 4 seconds, PLT<30×10^9/L;
Pregnant and lactating patients;
History of surgery for portal hypertension；History of prior EVL (endoscopic variceal ligation) or sclerotherapy, history of surgery for portal hypertension including portosystemic shunts, disconnection and spleen resection and transjugular intrahepatic portosystemic shunt;
Patients with severe diseases of vital organs such as heart, lung, kidney, brain, blood and nervous system;
Allergic to carvedilol and berberine;
Severe systemic diseases；
hemolytic anemia and lack of glucose - 6 - phosphate dehydrogenase patients
Refusal to participate in the study.