ClinicalTrials.gg
RecruitingNCT06449339BB_cACLDUpdated Oct 26, 2026

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

A Phase 4 interventional study of Carvedilol in Portal Hypertension, Hepatic Decompensation and Advanced Chronic Liver Disease, sponsored by Chinese University of Hong Kong. Recruiting at 1 site in Hong Kong. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-26.

Sponsored by Chinese University of Hong Kong · Phase 4, Interventional, and Treatment

From the registry’s dates

  • Started Jul 2024; still recruiting 2 years 3 months later.
Updated Oct 26, 2026Study documents postedSponsor changedGo to Updates ↓
Phase
Phase 4
Study type
Interventional
Enrollment
474
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed description

The study is a multi-centre, open-label, randomised controlled trial conducted in Prince of Wales Hospital, a tertiary academic hospital in Hong Kong, as well as other international study sites. Eligible patients will be randomised to NSBB arm (i.e. receiving carvedilol) or conventional arm (i.e. not receiving carvedilol), aiming to test the hypothesis that Baveno VII criteria-guided carvedilol treatment in compensated advanced chronic liver disease (cACLD) patients in grey zone or with clinically significant portal hypertension (CSPH) is superior to not treating them in the absence of high-risk varices (HRV), in terms of prevention of first occurrence of hepatic decompensation and mortality. Consecutive patients in the participating study sites with cACLD fulfilling the high-risk grey zone and CSPH criteria by LSM and platelet count will be invited to this study. The patients will undergo oesophagogastroduodenoscopy (OGD) for screening of oesophageal varices (OV). Those without HRV will be randomised into NSBB and conventional arms. Patients in the NSBB arm will be started on carvedilol. Those in the conventional arm will not receive NSBB as per current standard of practice. The expected accrual duration is 24 months with an interim analysis to be performed when all enrolled patients have reached 1 year of follow-up or the primary endpoint. The total follow-up duration is 5 years.

02

Conditions studied

  • Portal Hypertension
  • Hepatic Decompensation
  • Advanced Chronic Liver Disease

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Keywords

  • compensated advanced chronic liver disease
  • non-selective beta-blocker
  • Baveno VII
  • hepatic decompensation
03

In context

Hypertension, Portal

375 studies on the registry are indexed under Hypertension, Portal; 114 are open to participants now.

This study's planned enrollment of 474 is above the median of 60 across 231 interventional studies indexed under Hypertension, Portal.

Browse Hypertension, Portal studies →

Lead sponsor

Chinese University of Hong Kong is the lead sponsor of 1,454 studies on the registry; 474 are open to participants now.

Of its 6 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Aged 18 years of above
  • Established diagnosis of chronic liver disease(s) of the following etiologies

    • Alcohol-related liver disease (ARLD)
    • Chronic (CHB)
    • Chronic (CHC)
    • Metabolic dysfunction-associated steatotic liver disease (MASLD) § Non-obese ( \<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 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

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
  • 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 , 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 of less than 6 months
  • Pregnancy
  • Unable to obtain or refusal of from patient
Terms in these criteria, in plain language(8)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

COPD

Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
474 participants (estimated)

Study arms

  • Experimental
    non-selective beta-blocker (NSBB)

    oral carvedilol 6.25mg-50mg daily

    Drug: Carvedilol

  • No intervention
    Conventional

    Not on oral carvedilol

Interventions

  • 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.

06

What researchers measure

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

    Time frame: 5 years

Secondary outcomes

  1. Number of participants with development of each hepatic decompensation event

    Hepatic decompensation events include ascites, variceal bleeding and overt hepatic encephalopathy

    Time frame: 5 years

  2. Number of participants with development of hepatocellular carcinoma

    Development of hepatocellular carcinoma

    Time frame: 5 years

  3. Change in hepatic function in terms of Child-Pugh score

    Higher Child-Pugh score indicates poorer liver condition, vice versa

    Time frame: 5 years

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

    Higher MELD score indicates poorer liver condition, vice versa

    Time frame: 5 years

  5. Change in liver stiffness measurement (LSM) and spleen stiffness measurement (SSM)

    Change in liver and spleen stiffness measurements on transient elastography

    Time frame: 5 years

  6. Adverse events

    Any adverse events during the study period

    Time frame: 5 years

  7. Number of participants who survive until the last clinic visit

    Survival until end of study

    Time frame: 5 years

07

Study locations

1 of 1 sites recruiting
08

References and documents

Publications

  • 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. PubMed 35120736 ↗
  • 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. PubMed 33982942 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: Yes — Data may be shared upon reasonable request.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report

Time frame: 6 months after the first publication until 15 years after the end of the study

Access criteria: By email communication

09

Timeline

2 registry updates since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Jul 2024 (actual). Primary completion is estimated for Jul 2031, 84 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
May 29, 2024
First posted
Jun 10, 2024
StartActual
Jul 17, 2024
Primary completionEst.
Jul 30, 2031
CompletionEst.
Jul 30, 2031
Last update
Oct 26, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Documents
across 2 updates, Oct 22, 2026 – Oct 26, 2026
Sponsor
Collaborators added: Ruijin Hospital·E-DA Hospital·Asian Institute of Gastroenterology, India; collaborators removed: Singapore General Hospital·University of Palermo·Shanghai Jiao Tong University School of Medicine
Oct 22, 2026
Show all 2 updates
  1. Oct 26, 2026
  2. Oct 22, 2026
    Sponsor Collaborators added: Ruijin Hospital·E-DA Hospital·Asian Institute of Gastroenterology, India; collaborators removed: Singapore General Hospital·University of Palermo·Shanghai Jiao Tong University School of Medicine
    + 2 other changes: verification date and index terms

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT06449339
Collaborators
University of Malaya, Royal Prince Alfred Hospital, Sydney, Australia, Ruijin Hospital, E-DA Hospital, Asian Institute of Gastroenterology, India
Responsible party
Jimmy Che-To Lai (Clinical Assistant Professor, Chinese University of Hong Kong) — Principal investigator
First posted
Jun 10, 2024
Start date
Jul 17, 2024
Primary completion
Jul 30, 2031 (estimated)
Completion
Jul 30, 2031 (estimated)
Last update
Oct 26, 2026

Study contacts

Angel Chim, MSc
Contact
angelchim@cuhk.edu.hk
+852 3505 4205
Jimmy Che-To Lai, MB ChB
principal investigator · Chinese University of Hong Kong

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Carvedilol

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