Carvedilol for Prevention of Esophageal Varices Progression

Overview

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.

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Single (Participant)
  • Study Primary Completion Date: December 30, 2020

Detailed Description

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.

Interventions

  • Drug: 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. Target dose of 12.5 mg twice daily per day will be started after 2 weeks if systolic blood pressure does not fall below 90 mm Hg and HR 55/min.

Arms, Groups and Cohorts

  • Experimental: Carvedilol+ Nucleos(t)ide Analogues
    • Based on nucleoside analogue (NUCs), carvedilol will added to the patients. 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. Target dose of 12.5 mg twice daily per day will be started after 2 weeks if systolic blood pressure does not fall below 90 mm Hg and HR 55/min.
  • No Intervention: Nucleos(t)ide Analogues
    • Continuing take nucleoside analogue (NUCs) including lamivudine (LAM), adefovir dipivoxil (ADV), entecavir (ETV), telbivudine (TBV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF).

Clinical Trial Outcome Measures

Primary Measures

  • The progression Incidence of esophageal varices.
    • Time Frame: 2 years
    • 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.

Secondary Measures

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

Participating in This Clinical Trial

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 / min), 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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Beijing Friendship Hospital
  • Provider of Information About this Clinical Study
    • Principal Investigator: Xiaojuan Ou, Director of liver research center – Beijing Friendship Hospital
  • Overall Official(s)
    • Xiaojuan Ou, Principal Investigator, Beijing Friendship Hospital
  • Overall Contact(s)
    • Xiaoning Wu, +86-63138665, zdzxyyyy@163.com

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