Article Text
Abstract
Introduction Liver cirrhosis is the fifth largest cause of adult deaths, and a major complication, variceal bleeding is associated with a 1-year mortality of 40%. There is uncertainty on the first-line therapy for prevention of variceal bleeding owing to a lack of adequately powered trials comparing non-selective beta blockers, in particular carvedilol, with variceal band ligation.
Methods and analysis CALIBRE is a multicentre, pragmatic, randomised controlled, open-label trial with an internal pilot. The two interventions are carvedilol 12.5 mg od or variceal band ligation (VBL). Patients with liver cirrhosis and medium to large oesophageal varices that have never bled are eligible for inclusion. The primary outcome is any variceal bleeding within 1 year of randomisation. Secondary endpoints include time to variceal bleed, mortality, transplant-free survival, adverse events, complications of cirrhosis, health-related quality of life, use of healthcare resources, patient preference and use of alternative or crossover therapies. The sample size is 2630 patients over a 4-year recruitment period, across 66 hospitals in the UK.
Ethics and dissemination The study has been approved by a National Health Service (NHS) Research Ethics Committee (REC) (reference number 18/NE/0296). The results of this trial will be submitted for publication in a peer reviewed journal. Participants will be informed via a link to a preview of the publication. A lay summary will also be provided via email or posted to participants prior to publication (ISRCTN reference number: 73887615).
- cirrhosis
- portal hypertension
- oesophageal varices
- gastrointestinal bleeding
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Footnotes
Contributors DT is Chief Investigator and involved in all aspects of protocol design and lead author of the manuscript. PH, PR, IR and JF assisted in design of the protocol in particular clinical aspects. PD is lead for patient involvement in protocol design, with particular contributions to clinical aspects and consent pathways. In this role, he was assisted by JWF. JM is lead for the qualitative aspects of the protocol. In this role, he was assisted by CP. SJ is lead for heath economic aspects of the protocol. PB is involved in all aspects of protocol design, with particular attention to methodology. KH is lead for the statistical aspects of the protocol. MG, GS and KA reviewed the protocol with particular attention to management and operations. All authors reviewed and approved the final manuscript.
Funding This paper presents independent research funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme.
Disclaimer The views expressed are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request.