Carvedilol for Prevention of Esophageal Varices Progression

Study Overview
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Brief Summary
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Carvedilol has been shown to be more potent in decreasing portal hypertension to propranolol. But the efficacy of carvedilol to delay the growth of esophageal varices in chronic hepatitis B patients was unclear.

Detailed Description
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It has been concluded 40%-70% of chronic hepatitis B patients can achieve fibrosis/ cirrhosis reversion after effective anti-viral therapy. But there is still some patients progress to decompensation. Esophageal varices are the main complication of cirrhotic patients. Propranolol are widely used to prevent variceal bleeding in patients with large esophageal varices. It has been shown the efficacy of propranolol in the preventing of the progression from small to large varices reported no effect. Recently, carvedilol has been shown to be more potent in decreasing portal hypertension to propranolol. But the efficacy of carvedilol to delay the growth of esophageal varices in chronic hepatitis B patients was unclear. The purpose of this study is to demonstrate the efficacy of carvedilol in the preventing of the progression from small to large varices in hepatitis B patients.

Official Title
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Clinical Study of Carvedilol for the Prevention of the Progression of Esophageal Varices in Hepatitis B Related Cirrhotic Patients With Anti-Viral Therapy

Conditions
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Cirrhosis, Liver, Portal Hypertension

Intervention / Treatment
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* Drug: Carvedilol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female; HBV-related liver cirrhotic patients with at least two years of antiviral therapy; The presence of small or medium esophageal varices without red color sign; HBV-DNA<1×10E3 IU/ml Signature of informed consent Exclusion Criteria: Previous presence of decompensated cirrhosis including ascites, bleeding and HE (hepatic encephalopathy); 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 bpm), cardiogenic shock, hypotension (SBP < 90 mmHg), sick sinus syndrome, insulin dependent diabetes, peripheral vascular disease. Allergic to Carvedilol; Any malignancy that affects survival； Renal dysfunction； History of beta-blockers within last 3 months； 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； Severe systemic diseases； Refusal to participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carvedilol+ Nucleos(t)ide Analogues<br>Based on nucleoside analogue (NUCs), carvedilol will added to the patients. Carvedilol is started at a dose of 6.25 mg once daily. After 1 week, this will increased to a dose of 12.5 mg once daily. Target dose of 12.5 mg once daily will be maintained if systolic blood pressure does not fall below 90 mm Hg and HR 50 beats per minute. | Drug: Carvedilol<br>* Carvedilol is started at a dose of 6.25 mg once daily. After 1 week, this will increased to a dose of 12.5 mg once daily. Target dose of 12.5 mg once daily will be maintained if systolic blood pressure does not fall below 90 mm Hg and HR 50 beats per minute.<br>* Other names: Nucleos(t)ide Analogues;|
| No Intervention: Nucleos(t)ide Analogues<br>Continuing take nucleoside analogue (NUCs) including lamivudine (LAM), adefovir dipivoxil (ADV), entecavir (ETV), telbivudine (TBV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The progression Incidence of esophageal varices. | Progression of esophageal varices defines as follows: Varices developed from small(F1) to medium or large(F2/F3) Varices developed from medium(F2) to large(F3) Bleeding from esophageal varices. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of liver cirrhosis decompensation | Cumulative rate of liver decompensation (including ascites,hepatic encephalopathy) after 2 year. | 2 years | 
| The incidence of hepatic cellular carcinoma, death or liver transplantation. | Cumulative rate of hepatic cellular carcinoma, death or liver transplantation after 2 year. | 2 years | 
| The progression rate of non-invasive scores (Child-Pugh、MELD、APRI、FIB-4 score). | The progression rate of Child-Pugh、MELD、APRI、FIB-4 score after 2 years. | 2 years | 
| The dynamic change of liver stiffness quantified by transient elastography. | The dynamic change of liver stiffness quantified by transient elastography after 2 years. | 2 years | 
| The dynamic change of hemodynamics parameter | The dynamic change of hemodynamics (HR and mean arterial pressure) after 2 years. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Portal Hypertension, Esophageal varices, Carvedilol