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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04543643
Recruitment Status : Not yet recruiting
First Posted : September 10, 2020
Last Update Posted : October 25, 2021
Sponsor:
Information provided by (Responsible Party):
Tianjin Second People's Hospital

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 288 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel 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
Estimated Study Start Date : November 1, 2021
Estimated Primary Completion Date : October 31, 2023
Estimated Study Completion Date : October 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Endoscopy
Drug Information available for: Carvedilol

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.




Primary Outcome Measures :
  1. The progression Incidence of esophageal varices [ Time Frame: 1 year ]
    progression of esophagogastric varices under gastroscopy and/or endoscopic ultrasound


Secondary Outcome Measures :
  1. The incidence of liver cirrhosis decompensation [ Time Frame: 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)

  2. HCC, death or liver transplantation [ Time Frame: 1 year ]
    The incidence of hepatic cellular carcinoma, death or liver transplantation



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04543643


Contacts
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Contact: Han Ping, bachelor 13652139315 13652139315@163.com
Contact: Li Jia, professor 13302106853 18622663700@163.com

Locations
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China, Tianjin
Tianjin Second People's Hospital
Tianjin, Tianjin, China, 300192
Contact: Han Ping, bachelor    +8613652139315    13652139315@163.com   
Contact: Li Jia, professor    +86133021006853    18622663700@163.com   
Sponsors and Collaborators
Tianjin Second People's Hospital
Publications of Results:

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Responsible Party: Tianjin Second People's Hospital
ClinicalTrials.gov Identifier: NCT04543643    
Other Study ID Numbers: Tianjin2PH
First Posted: September 10, 2020    Key Record Dates
Last Update Posted: October 25, 2021
Last Verified: October 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Tianjin Second People's Hospital:
gastroesophageal varices
cirrhosis
carvedilol
berberine
Endoscopic ultrasonography
gut microbiota
portal hypertension
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Hepatitis B
Hepatitis
Liver Cirrhosis
Fibrosis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Infections
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Blood-Borne Infections
Communicable Diseases
Flaviviridae Infections
Hepadnaviridae Infections
DNA Virus Infections
Pathologic Processes
Carvedilol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antihypertensive Agents
Antioxidants
Protective Agents