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Carvedilol for Prevention of Esophageal Varices Progression (Carvedilol)

Primary Purpose

Cirrhosis, Liver, Portal Hypertension

Status
Active
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Carvedilol
Sponsored by
Beijing Friendship Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cirrhosis, Liver focused on measuring Portal Hypertension, Esophageal varices, Carvedilol

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Beijing Ditan Hospital Capital Medical University
  • Peking University First Hospital
  • Peking University People's Hospital
  • Beijing Friendship Hospital
  • Zhongshan Hospital Fudan University
  • The First Affiliated Hospital of Shanghai Jiao Tong University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Carvedilol+ Nucleos(t)ide Analogues

Nucleos(t)ide Analogues

Arm Description

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.

Continuing take nucleoside analogue (NUCs) including lamivudine (LAM), adefovir dipivoxil (ADV), entecavir (ETV), telbivudine (TBV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

The incidence of liver cirrhosis decompensation
Cumulative rate of liver decompensation (including ascites,hepatic encephalopathy) after 2 year.
The incidence of hepatic cellular carcinoma, death or liver transplantation.
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).
The progression rate of Child-Pugh、MELD、APRI、FIB-4 score after 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.
The dynamic change of hemodynamics parameter
The dynamic change of hemodynamics (HR and mean arterial pressure) after 2 years.

Full Information

First Posted
May 3, 2018
Last Updated
November 29, 2022
Sponsor
Beijing Friendship Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03736265
Brief Title
Carvedilol for Prevention of Esophageal Varices Progression
Acronym
Carvedilol
Official Title
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
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 9, 2017 (Actual)
Primary Completion Date
November 30, 2022 (Anticipated)
Study Completion Date
December 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beijing Friendship Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cirrhosis, Liver, Portal Hypertension
Keywords
Portal Hypertension, Esophageal varices, Carvedilol

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
240 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Carvedilol+ Nucleos(t)ide Analogues
Arm Type
Experimental
Arm Description
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.
Arm Title
Nucleos(t)ide Analogues
Arm Type
No Intervention
Arm Description
Continuing take nucleoside analogue (NUCs) including lamivudine (LAM), adefovir dipivoxil (ADV), entecavir (ETV), telbivudine (TBV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF).
Intervention Type
Drug
Intervention Name(s)
Carvedilol
Other Intervention Name(s)
Nucleos(t)ide Analogues
Intervention Description
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.
Primary Outcome Measure Information:
Title
The progression Incidence of esophageal varices.
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
The incidence of liver cirrhosis decompensation
Description
Cumulative rate of liver decompensation (including ascites,hepatic encephalopathy) after 2 year.
Time Frame
2 years
Title
The incidence of hepatic cellular carcinoma, death or liver transplantation.
Description
Cumulative rate of hepatic cellular carcinoma, death or liver transplantation after 2 year.
Time Frame
2 years
Title
The progression rate of non-invasive scores (Child-Pugh、MELD、APRI、FIB-4 score).
Description
The progression rate of Child-Pugh、MELD、APRI、FIB-4 score after 2 years.
Time Frame
2 years
Title
The dynamic change of liver stiffness quantified by transient elastography.
Description
The dynamic change of liver stiffness quantified by transient elastography after 2 years.
Time Frame
2 years
Title
The dynamic change of hemodynamics parameter
Description
The dynamic change of hemodynamics (HR and mean arterial pressure) after 2 years.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaojuan Ou
Organizational Affiliation
Beijing Friendship Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Ditan Hospital Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100015
Country
China
Facility Name
Peking University First Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100034
Country
China
Facility Name
Peking University People's Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100044
Country
China
Facility Name
Beijing Friendship Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100050
Country
China
Facility Name
Zhongshan Hospital Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
The First Affiliated Hospital of Shanghai Jiao Tong University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
201620
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Carvedilol for Prevention of Esophageal Varices Progression

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