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Randomized Controlled Trial
. 2025 Jun;61(11):1740-1754.
doi: 10.1111/apt.70080. Epub 2025 Apr 16.

Clinical Trial: A Multicentre Randomised Controlled Trial of Carvedilol Versus Variceal Band Ligation in Primary Prevention of Variceal Bleeding in Liver Cirrhosis (CALIBRE Trial)

Dhiraj Tripathi  1   2 , Kelly Handley  3 , Lisa Holden  3 , Zainab Abdali  4 , Sue Jowett  4 , Jonathan Mathers  5 , Christopher Poyner  6 , Paul Richardson  7 , James Ferguson  1   2 , Ian Rowe  8   9 ; CALIBRE trial collaborative group
Collaborators, Affiliations
Randomized Controlled Trial

Clinical Trial: A Multicentre Randomised Controlled Trial of Carvedilol Versus Variceal Band Ligation in Primary Prevention of Variceal Bleeding in Liver Cirrhosis (CALIBRE Trial)

Dhiraj Tripathi et al. Aliment Pharmacol Ther. 2025 Jun.

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.

Trial registration: ISRCTN73887615.

Keywords: gastrointestinal bleeding; liver cirrhosis; oesophageal varices; portal hypertension.

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Conflict of interest statement

Dhiraj Tripathi is the principal investigator of drug therapy trials in portal hypertension sponsored by Boehringer Ingelheim and AstraZeneca (payments to institution). Dhiraj Tripathi is the principal investigator of Beta‐blockers or placebo for primary prophylaxis of oesophageal varices (BOPPP study) funded by the National Institute for Health and Care Research (NIHR) HTA programme (payments to institution).

Figures

FIGURE 1
FIGURE 1
Consort flow diagram. Carvedilol, carvedilol 12.5 mg once daily orally. VBL, variceal band ligation as recommended in BSG guidelines.
FIGURE 2
FIGURE 2
Kaplan Meier: time to first variceal bleed. HR, hazard ratio; VBL, variceal band ligation.
See this image and copyright information in PMC

References

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