Table 2 Eligibility criteria

Inclusion criteria

 Cirrhosis and portal hypertension, defined by any 2 of the following:

  - Characteristic clinical examination findings; one or more of

   - Characteristic liver function tests

   - Haematological panel

   - Coagulation profile abnormalities

  - Characteristic radiological findings; one or more of

   - Heterogeneous liver with irregular contour

   - Splenomegaly

   - Ascites

   - Varices

   - Recanalized umbilical vein

  - FibroScan liver stiffness measurement > 15 kPa without other explanation

  - Fibrosis score > ISHAK stage 4 on liver biopsy

 Small oesophageal varices diagnosed within the last 6 months^a

 Not received a beta-blocker in the last week

 Capacity to provide informed consent

Exclusion criteria

 Non-cirrhotic portal hypertension

 Current medium/large oesophageal varices (defined as > 5 mm in diameter)

 Previous medium/large oesophageal varices, which decreased in size with curative therapy

 Gastric (IGV and GOV2), duodenal, rectal or other ectopic varices with or without evidence of recent bleeding. For gastric varices, this includes the following: IGV-1 and IGV-2 (isolated gastric varices) and GOV2 (gastric varices continuing into the cardia)

  ⦁ [GOV1 (gastric varices continuing into the lesser curve) are not an exclusion if present with small oesophageal varices]

 Previous variceal haemorrhage

 Previous band ligation or glue injection of oesophageal and/or gastric varices

 Red signs accompanying small oesophageal varices at endoscopy

 Known intolerance to beta blockers

 Contraindications to beta-blocker use: Heart rate < 50 bpm, known 2nd degree or higher heart block, sick sinus syndrome, systolic blood pressure < 85 mmHg, chronic airways obstruction (asthma/COPD), Floppy Iris Syndrome, CYP2D6 poor metaboliser, history of cardiogenic shock, history of severe hypersensitivity reaction to beta-blockers, untreated phaeochromocytoma, severe peripheral vascular disease, prinzmetal angina and NYHA IV heart failure

 Unable to provide informed consent^a

 Child–Pugh C cirrhosis^a

 Already receiving a beta-blocker for another reason that cannot be discontinued

 Graft cirrhosis post liver transplantation

 Evidence of active malignancy without curative therapy planned

 Pregnant or lactating women^a

 Women of child bearing potential not willing to use adequate contraception during the period of IMP dosing (if relevant)

 Patients who have been on a CTIMP within the previous 3 months

 Clinical symptoms consistent with COVID-19 at the time of randomisation