RecruitingPhase 4NCT06449339

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

Baveno VII Criteria-guided Initiation of Non-selective Beta Blocker in Patients With Compensated Advanced Chronic Liver Disease to Reduce Hepatic Decompensation: an Open-label Randomised Controlled Trial

Sponsor

Chinese University of Hong Kong

Enrollment

474 participants

Start Date

Jul 17, 2024

Study Type

INTERVENTIONAL

Conditions

Advanced Chronic Liver Disease Portal Hypertension Hepatic Decompensation

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria13

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)

Exclusion Criteria17

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
Pregnancy
Unable to obtain or refusal of informed consent from patient

Interventions

DRUGCarvedilol

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.