Extension Study of Carvedilol RCT Study

Study Overview
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Brief Summary
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Patients who have completed 2-years treatment in RCT Study of carvedilol will receive another 2-years extension therapy, aiming to investigate the long-term efficacy of carvedilol for the prevention of esophageal varices in treated HBV cirrhotic patients.

Detailed Description
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Carvedilol has been shown to be more potent in decreasing portal hypertension than propranolol. But the efficacy of carvedilol to prevent esophageal varices progression in nucleoside analogue (NUCs) treatment HBV related cirrhotic patients was unclear. Previous RCT study aimed to explore the effects of carvedilol for the prevention of the esophageal varices progression on HBV cirrhotic patients with anti-viral therapy has been conducted (NCT03736265). Patients who have completed 2-years treatment in RCT Study of carvedilol will receive another 2-years extension therapy, aiming to investigate the long-term efficacy of carvedilol for the prevention of esophageal varices in treated HBV cirrhotic patients. Patients were allocated according to the outcome of EDGs at 2-year during RCT study. Patients will be assessed at baseline and every six months for blood cell count, liver function test, HBVDNA, AFP, prothrombin time, liver ultrasonography, and Fibroscan. A third EGDs will be performed at 4-year.

Official Title
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Extension Study of Carvedilol for the Prevention of the Esophageal Varices Progression on HBV Cirrhotic Patients With Anti-Viral Therapy

Conditions
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Liver Cirrhosis, Portal Hypertension

Intervention / Treatment
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* Drug: Carvedilol 12.5 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who completed the 2-year RCT study of carvedilol in HBV cirrhotic patients with anti-viral therapy; Subjects who are willing to participate the extension study. Exclusion Criteria: Subjects who refused to receive 2-year EGD examination during the previous RCT study; Subjects who could not compliance with the protocol judged by investigators; Subjects who are not suitable for the study judged by investigators.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carvedilol+ NUCs therapy<br>Patients randomized to Carvedilol combined with NUCs group during the previous 2-year treatment of RCT study; Patients showed the progression of esophageal varices in NUCs group during the 2-year treatment of RCT study. Based on nucleoside analogue (NUCs), carvedilol will be added to the patients. Carvedilol is started at a dose of 6.25 mg once per day, and will increase to a dose of 12.5 mg once per day after 1 week. Target dose will be maintained at 12.5 mg once per day if patients with systolic blood pressure not lower than 90 mm Hg and HR no less than 50 beats/min. | Drug: Carvedilol 12.5 MG<br>* Carvedilol is started at a dose of 6.25 mg once per day, and will increase to a dose of 12.5 mg once per day after 1 week. Target dose will be maintained at 12.5 mg once per day if patients with systolic blood pressure not lower than 90 mm Hg and HR no less than 50 beats/min.<br>* Other names: Nucleos(t)ide Analogues;|
| No Intervention: NUCs therapy<br>Continuing take single or combined 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 after 4-year therapy | 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) New-onset red sign without change in the degree of varices. Bleeding from esophageal varices. | 4-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of liver cirrhosis decompensation | Cumulative rate of liver cirrhosis decompensation, including bleeding, ascites, hepatic encephalopathy, ect. | 4-year | 
| The incidence of hepatic cellular carcinoma, death or liver transplantation. | Cumulative rate of hepatic cellular carcinoma, death or liver transplantation. | 4-year | 
| The change of non-invasive assessment score reflecting liver fibrosis. | Higher scores mean a worse outcome. | 4-year | 
| The change of non-invasive assessment score reflecting liver function. | Higher scores mean a worse outcome. | 4-year | 
| The dynamic change of liver stiffness quantified by transient elastography. | The dynamic change of liver stiffness quantified by transient elastography. | 4-year | 

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