Using carvedilol to prevent liver complications in patients with 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

This study is testing if the medication carvedilol can help prevent serious liver problems in people with advanced chronic liver disease and high blood pressure in the liver.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 474 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chinese University of Hong Kong (other)
• Locations: 1 site (Hong Kong)
• Trial ID: NCT06449339 on ClinicalTrials.gov

What this trial studies

This randomized controlled trial evaluates the effectiveness of carvedilol, a non-selective beta-blocker, in patients with compensated advanced chronic liver disease who have clinically significant portal hypertension. Participants will be assigned to either receive carvedilol or not for a duration of five years, with regular follow-ups including blood tests and liver imaging. The study aims to determine if carvedilol can reduce the risk of hepatic decompensation and mortality in patients without high-risk varices. Conducted at multiple centers, including the Prince of Wales Hospital in Hong Kong, the trial will follow patients for a total of five years to assess outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with compensated advanced chronic liver disease and clinically significant portal hypertension, but without high-risk varices.

Not a fit: Patients with high-risk varices will not benefit from this study as they are excluded from participation.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of liver complications and mortality in patients with advanced chronic liver disease.

How similar studies have performed: Other studies have shown promising results with non-selective beta-blockers in similar patient populations, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* 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 Criteria:

* 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

Where this trial is running

Hong Kong

• Prince of Wales Hospital, The Chinese University of Hong Kong — Hong Kong, Hong Kong (RECRUITING)

Study contacts

• Principal investigator: Jimmy Che-To Lai, MB ChB — Chinese University of Hong Kong
• Study coordinator: Angel Chim, MSc

Conditions: Portal Hypertension, Hepatic Decompensation, Advanced Chronic Liver Disease, compensated advanced chronic liver disease, non-selective beta-blocker, Baveno VII, hepatic decompensation