Beta-blockers or placebo for primary prophylaxis of oesophageal varices trial

Phase 4

• Conditions: Participants with cirrhosis and small varices without evidence of previous bleeding; Circulatory System; Oesophageal varices

• Registration Number: ISRCTN10324656
• Lead Sponsor: King’s College Hospital NHS Foundation Trust

Brief Summary

2022 Other publications in https://pubmed.ncbi.nlm.nih.gov/35113923/ results of the embedded qualitative study (added 04/02/2022) 2022 Other publications in https://pubmed.ncbi.nlm.nih.gov/36251653/ results of the embedded qualitative study (added 18/10/2022) 2024 Protocol article in https://doi.org/10.1186/s13063-024-08063-3 (added 17/04/2024)

Detailed Description

Not available

Study Timeline

• Study Start: 2018-12-04
• Last Update Posted: 9 September 2024
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 763

Inclusion Criteria

1. Age >18 years
2. Cirrhosis and portal hypertension, defined by any two of the following:
2.1. Characteristic clinical examination findings; one or more of:
2.1.1. Jaundice, ascites, caput medusae, spider naevi, palmar erythema, asterixis
2.2. Characteristic liver function tests, haematological panel and coagulation profile abnormalities
2.2.1. hyperbilirubinaemia (serum total bilirubin > 30 umol/l)
2.2.2. thrombocytopenia (platelet count <120 x109 / L)
2.2.3.international normalised raio (INR) > 1.5
NB These blood tests may be normal in well compensated cirrhosis – if cirrhosis is confirmed on other investigations, normal blood tests suggest well compensated disease.
2.3. Characteristic radiological findings; one or more of:
2.3.1. Heterogeneous, small liver with irregular contour
2.3.2. Splenomegaly
2.3.3. Ascites
2.3.4. Varices
2.3.5. Recanalized umbilical vein
2.4. Fibrosis score > stage 4 on liver biopsy
2.5. FibroScan liver stiffness measurement >15 kPa without other explanation
3. Small oesophageal varices – defined as <5mm in diameter or completely disappear on moderate insufflation at gastroscopy within the last 3 months
4. Not received a beta-blocker in the last week
5. Capacity to provide informed consent
6. Fluent in the English Language

Exclusion Criteria

1. Non-cirrhotic portal hypertension
2. Medium/large oesophageal varices (current or history of)
3. Isolated gastric, duodenal, rectal varices with or without evidence of recent bleeding
4. Previous variceal haemorrhage
5. Known intolerance to beta blockers
6. Contraindication to beta blocker use:
6.1. Heart rate <50 bpm
6.2. Known 2nd degree or higher heart block
6.3. Sick sinus syndrome
6.4. Systolic blood pressure <85mm Hg
6.5. Chronic airways obstruction (asthma/COPD)
6.6. Floppy Iris Syndrome
6.7. CYP2D6 Poor Metaboliser
6.8. Cardiogenic shock
6.9. History of severe hypersensitivity reaction to beta blockers
6.10. Untreated phaeochromocytoma
6.11. Severe peripheral vascular disease
6.12. Prinzmetal angina
6.13. NYHA IV heart failure
7. Unable to provide informed consent
8. Child Pugh C cirrhosis
9. Already receiving a beta-blocker for another reason that cannot be discontinued
10. Pregnant or lactating women
11. Graft cirrhosis post liver transplantation
12. Evidence of active malignancy without curative therapy planned

Study & Design

• Study Type: Interventional
• Study Design: Not specified