Portal HypertensionPhase 4BB_cACLDNCT06449339
Non-selective Beta-blocker in Compensated Advanced Chronic Liver Disease
A Phase 4 study testing Carvedilol in people with Portal Hypertension and Hepatic Decompensation, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Portal Hypertension, Hepatic Decompensation, Advanced Chronic Liver Disease
- What is being tested?
- Carvedilol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 474 participants
- Where
- 1 siteHong Kong
- Study dates
- 17 Jul 2024to 30 Jul 2031
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 13Show fewer
- 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)
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Hong Kong1 site, 1 recruiting
- Recruiting
Prince of Wales Hospital, The Chinese University of Hong Kong
Hong Kong
Jimmy Che-To Lai, jimmyctlai@cuhk.edu.hk
About this study
Official title: 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
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:
Read more
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.
- Being tested
- Carvedilol
- Keywords
- compensated advanced chronic liver disease, non-selective beta-blocker, Baveno VII, hepatic decompensation
- Medical subject headings
- Hypertension, Portal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| non-selective beta-blocker (NSBB) | Experimental | oral carvedilol 6.25mg-50mg daily Receives: Drug: Carvedilol |
| Conventional | No intervention | Not on oral carvedilol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 5 years
Secondary outcomes (7)
Number of participants with development of each hepatic decompensation event
Hepatic decompensation events include ascites, variceal bleeding and overt hepatic encephalopathy
Measured: 5 years
Number of participants with development of hepatocellular carcinoma
Development of hepatocellular carcinoma
Measured: 5 years
Change in hepatic function in terms of Child-Pugh score
Higher Child-Pugh score indicates poorer liver condition, vice versa
Measured: 5 years
Change in hepatic function in terms of model for end-stage liver disease (MELD) score
Higher MELD score indicates poorer liver condition, vice versa
Measured: 5 years
Change in liver stiffness measurement (LSM) and spleen stiffness measurement (SSM)
Change in liver and spleen stiffness measurements on transient elastography
Measured: 5 years
Adverse events
Any adverse events during the study period
Measured: 5 years
Number of participants who survive until the last clinic visit
Survival until end of study
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2024
- Study start17 Jul 2024
- Primary completion30 Jul 2031 (estimated)
- Study completion30 Jul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Portal HypertensionStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 474 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- University of Malaya, Royal Prince Alfred Hospital, Sydney, Australia, Ruijin Hospital, E-DA Hospital, Asian Institute of Gastroenterology, India
- Responsible party
- Principal investigator, Jimmy Che-To Lai, Chinese University of Hong Kong
- Investigators
- Jimmy Che-To Lai, MB ChB, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06449339
- Sponsor's protocol ID
- 2023.521-T
- Acronym
- BB_cACLD
- Status last verified
- Oct 2026
- First submitted
- 29 May 2024
- Last updated
- 22 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data may be shared upon reasonable request.
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 35120736Pons 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