Clinical trial: a multicentre randomised controlled trial of carvedilol versus variceal band ligation in primary prevention of variceal bleeding in liver cirrhosis (CALIBRE trial)
Tripathi, Dhiraj Handley, Kelly Holden, Lisa Abdali, Zainab Jowett, Sue Mathers, Jonathan Poyner, Christopher Richardson, Paul Ferguson, James Rowe, Ian
Tripathi, Dhiraj
Handley, Kelly
Holden, Lisa
Abdali, Zainab
Jowett, Sue
Mathers, Jonathan
Poyner, Christopher
Richardson, Paul
Ferguson, James
Rowe, Ian
Affiliation
University Hospitals Birmingham NHS Foundation Trust; University of Birmingham; Royal Liverpool Hospital NHS Foundation Trust; University of Leeds; Leeds Teaching Hospitals NHS Trust
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Publication date
2025-04-16
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Abstract
Background: The superior efficacy of non-selective beta-blockers (NSBB) compared with variceal band ligation (VBL) in the primary prevention of variceal bleeding is uncertain.
Aim: To compare carvedilol versus VBL for primary prevention of variceal bleeding.
Methods: CALIBRE was an investigator-initiated, multicentre, randomised, controlled, open-label trial. Participants were randomly assigned to 12.5 mg carvedilol once daily or VBL. Inclusion criteria were cirrhosis and medium to large oesophageal varices that had not bled. The primary outcome is any variceal bleeding within 1 year of randomisation. Secondary outcomes include survival, other complications of cirrhosis, quality of life, cost-effectiveness and adverse events. Recruitment closed early, mainly due to the impact of the pandemic.
Results: 265 participants (10% of the intended sample size) from 52 sites were randomised to carvedilol (n = 133) or VBL (n = 132) between 22 January 2019 and 31 August 2022. 5/133 participants (3.8%) in the carvedilol arm vs. 10/132 participants (7.6%) in the VBL arm experienced variceal bleeding (risk ratio 0.50 (95% confidence interval [CI]; 0.17-1.41); risk difference - 0.038 (95% CI; -0.094-0.017)). Serious adverse events occurred in one participant in each treatment arm, with no treatment-related deaths. Of the secondary outcomes, there were no statistically significant differences. Carvedilol was cheaper and resulted in slightly more quality-adjusted life years than VBL.
Conclusions: The early terminated and, thus, underpowered CALIBRE trial showed no difference between carvedilol and VBL in the primary prevention of variceal bleeding in patients with cirrhosis and medium-to large-sized oesophageal varices. No untoward safety concerns were noted.
Citation
Tripathi D, Handley K, Holden L, Abdali Z, Jowett S, Mathers J, Poyner C, Richardson P, Ferguson J, Rowe I; CALIBRE trial collaborative group. Clinical Trial: A Multicentre Randomised Controlled Trial of Carvedilol Versus Variceal Band Ligation in Primary Prevention of Variceal Bleeding in Liver Cirrhosis (CALIBRE Trial). Aliment Pharmacol Ther. 2025 Jun;61(11):1740-1754. doi: 10.1111/apt.70080. Epub 2025 Apr 16.
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Article