Non-selective Beta-blocker in Compensated Advanced Chronic Liver Disease

NCT06449339 | Recruiting Phase 4

• 1 other identifier: 2023.521-T
• Study Type: interventional
• Target: 474
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this randomised controlled trial is to evaluate the effect of carvedilol (a non-selective beta-blocker) in patients with compensated advanced chronic liver disease under clinically significant portal hypertension or the grey zone of Baveno VII criteria. The main question it aims to answer is: Does carvedilol reduce hepatic decompensation and mortality in these patients despite the absence of varices needing treatment. Researchers will compare carvedilol to no carvedilol to see if carvedilol can prevent hepatic decompensation and mortality. Participants will either take carvedilol or not taking carvedilol for 5 years with regular clinic visit for checkups and investigations, including blood tests, ultrasonography of the liver, upper gastrointestinal endoscopy, transient elastography.

Conditions

Portal Hypertension; Hepatic Decompensation; Advanced Chronic Liver Disease

Keywords

compensated advanced chronic liver disease; non-selective beta-blocker; Baveno VII; hepatic decompensation

Outcome Measures

Primary Outcomes (1)

• composite of incident high-risk varices (HRV), hepatic decompensation or death

  HRV is defined by moderate to large oesophageal varices (OV) or OV with red wale sign. Hepatic decompensation is defined by the presence of ascites, variceal bleeding or overt hepatic encephalopathy

  5 years

Secondary Outcomes (7)

• Number of participants with development of each hepatic decompensation event

  5 years

• Number of participants with development of hepatocellular carcinoma

  5 years

• Change in hepatic function in terms of Child-Pugh score

  5 years

• Change in hepatic function in terms of model for end-stage liver disease (MELD) score

  5 years

• Change in liver stiffness measurement (LSM) and spleen stiffness measurement (SSM)

  5 years

Study Arms (2)

non-selective beta-blocker (NSBB)

EXPERIMENTAL

oral carvedilol 6.25mg-50mg daily

Drug: Carvedilol

Conventional

NO INTERVENTION

Not on oral carvedilol

Interventions

Carvedilol DRUG

Patients in the NSBB arm will receive generic carvedilol. The starting dose of oral carvedilol is 6.25mg daily (to be taken once or twice per day) and can be adjusted at each scheduled visit (either by increasing the dosage or frequency of dose administration) according to patients' tolerance, as well as the blood pressure and pulse rate that the systolic blood pressure should be not lower than 90 mmHg and pulse rate not lower than 55 beats per minute. The dosage of carvedilol can also be titrated or discontinued at unscheduled visit according to patient's condition. In case carvedilol is discontinued, it can be resumed from the starting dose at next scheduled visit if there is no contraindication for carvedilol. The dose of carvedilol will be kept at 6.25-12.5mg per day unless there are additional non-hepatic indications such as arterial hypertension or cardiac disease warranting higher carvedilol dosage. The maximum allowed dose of carvedilol is 50mg daily as per drug instruction.

non-selective beta-blocker (NSBB)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years of above
• Established diagnosis of chronic liver disease(s) of the following etiologies
• Alcohol-related liver disease (ARLD)
• Chronic hepatitis B (CHB)
• Chronic hepatitis C (CHC)
• Metabolic dysfunction-associated steatotic liver disease (MASLD) § Non-obese (BMI \<30kg/m2) and obese (BMI ≥30 kg/m2)
• In high-risk grey zone or CSPH, by Baveno VII criteria (for ARLD, CHB, CHC and non-obese MASLD) or ANTICIPATE-NASH model (for obese MASLD) within 6 months from screening
• Baveno VII criteria (for ARLD, CHB, CHC and non-obese MASLD)
• LSM ≥25 kPa (CSPH)
• LSM ≥20 kPa - \<25 kPa and platelet count \<150 x 10\^9/L; or LSM ≥15 kPa - \<20 kPa and platelet count \<110 x 10\^9/L (high-risk grey zone)
• ANTICIPATE-NASH model (for obese MASLD)
• Predictive probability for CSPH \>90% (CSPH)
• Predictive probability for CSPH ≥60% - \<90% (high-risk grey zone)

You may not qualify if:

• Presence of high-risk varices (HRV) (i.e. moderate to large oesophageal varices \[OV\] or OV with red wale sign) found in OGD
• Current use of non-selective beta-blocker (NSBB) or any use of NSBB within 6 months before
• Use of selective beta blocker, such as atenolol or metoprolol, is not excluded
• Selective beta-blocker will be switched to carvedilol in NSBB arm, and will be kept unchanged in conventional arm if there is clinical need for the selective beta-blocker
• Contraindication to NSBB (e.g. Type II/III heart block or baseline bradycardia \<60/minute, hypotension with systolic blood pressure (SBP) \<100 mmHg, asthma, poorly controlled chronic obstructive pulmonary disease, and peripheral vascular disease)
• Current use of nitrated drugs or any use of nitrated drugs within 6 months before
• o Use of sublingual nitrate, such as glyceryl trinitrate, is not excluded
• Contraindication to OGD (e.g. Intestinal perforation or obstruction)
• Current or history of decompensated liver cirrhosis (i.e. Child's C cirrhosis, prior decompensating events such as ascites, variceal bleeding, hepatic encephalopathy and hepatorenal syndrome)
• o Child's B cirrhosis without decompensating events is not excluded
• Current or history of hepatocellular carcinoma (HCC)
• Current or history of portal vein thrombosis
• Transjugular intrahepatic portosystemic shunt (TIPS)
• Liver transplantation
• Serious medical illness with limited life expectancy of less than 6 months

Sponsors & Collaborators

• Chinese University of Hong Kong: lead
• Singapore General Hospital: collaborator
• University of Palermo: collaborator
• University of Malaya: collaborator
• Shanghai Jiao Tong University School of Medicine: collaborator
• Royal Prince Alfred Hospital, Sydney, Australia: collaborator

Study Sites (1)

Prince of Wales Hospital, The Chinese University of Hong Kong

Hong Kong, Hong Kong

RECRUITING

Related Publications (2)

• de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C; Baveno VII Faculty. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022 Apr;76(4):959-974. doi: 10.1016/j.jhep.2021.12.022. Epub 2021 Dec 30.

  PMID: 35120736 BACKGROUND

• Pons M, Augustin S, Scheiner B, Guillaume M, Rosselli M, Rodrigues SG, Stefanescu H, Ma MM, Mandorfer M, Mergeay-Fabre M, Procopet B, Schwabl P, Ferlitsch A, Semmler G, Berzigotti A, Tsochatzis E, Bureau C, Reiberger T, Bosch J, Abraldes JG, Genesca J. Noninvasive Diagnosis of Portal Hypertension in Patients With Compensated Advanced Chronic Liver Disease. Am J Gastroenterol. 2021 Apr;116(4):723-732. doi: 10.14309/ajg.0000000000000994.

  PMID: 33982942 BACKGROUND

MeSH Terms

Conditions

Hypertension, Portal

Interventions

Carvedilol

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Study Officials

• Jimmy Che-To Lai, MB ChB

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Angel Chim, MSc

CONTACT

+852 3505 4205; angelchim@cuhk.edu.hk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: May 29, 2024
• First Posted: June 10, 2024
• Study Start: July 17, 2024
• Primary Completion (Estimated): July 30, 2031
• Study Completion (Estimated): July 30, 2031
• Last Updated: June 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 6 months after the first publication until 15 years after the end of the study
• Access Criteria: By email communication

Locations

HK (1)