Carvedilol for Prevention of Esophageal Varices Progression (Carvedilol)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Portal Hypertension; Cirrhosis, Liver
• Intervention / Treatment: Drug: Carvedilol

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.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
    • Beijing, Beijing, China, 100015
      • Beijing Ditan Hospital Capital Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital Fudan University
    • Shanghai, Shanghai, China, 201620
      • The First Affiliated Hospital of Shanghai Jiao Tong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 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; 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.; Other Names: Nucleos(t)ide Analogues
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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Investigators: Principal Investigator: Xiaojuan Ou, Beijing Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2017
• Primary Completion (Anticipated): November 30, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: May 3, 2018
• First Submitted That Met QC Criteria: November 7, 2018
• First Posted (Actual): November 9, 2018

Study Record Updates

• Last Update Posted (Actual): December 1, 2022
• Last Update Submitted That Met QC Criteria: November 29, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Carvedilol; Portal Hypertension; Esophageal varices
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Gastrointestinal Diseases; Liver Diseases; Fibrosis; Esophageal Diseases; Hypertension; Liver Cirrhosis; Esophageal and Gastric Varices; Hypertension, Portal; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Protective Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Carvedilol
• Other Study ID Numbers: 2017ZX10203202003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No