Variceal bleeding in liver cirrhosis Digestive System Variceal bleeding in liver cirrhosis
Conditions
Interventions
After participant eligibility has been confirmed and informed consent has been received, the participant can be randomised into the trial. A Randomisation Form will be provided to investigators and wi
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Liver cirrhosis as defined clinically, radiologically (USS and transient elastography), or on histology 2. Medium varices (Grade II varices that do not flatten on air insufflation and do not occlude the lumen) and large varices (Grade III varices which are larger than Grade II varices and occupy the whole lumen) that have never bled as defined in the BSG guidelines 3. Aged 18 years or older
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 24/11/2021: 1. Age <18 years 2. Pregnant or lactating women 3. Known intolerance or contraindications to beta-blockers including asthma 4. Current or past history of non-selective beta-blocker use (such as carvedilol, nadolol or propranolol) 5. Current or history of variceal band ligation 6. Presence of malignancy or systemic disease that significantly affects 1-year survival 7. Unable to give informed consent 8. Diagnosed with acute alcoholic hepatitis at the point of randomisation 9. Patients with surgical or radiological portosystemic shunts such as transjugular portosystemic stent-shunt (TIPSS) 10. Previous organ transplantation Previous exclusion criteria: 1. Pregnant or lactating women 2. Known allergy to carvedilol 3. Already on non-selective beta-blockers that could not be discontinued 4. Presence of malignancy or systemic disease that significantly affects 1-year survival 5. Unable to give informed consent 6. Contraindications to beta-blockers including asthma 7. Acute alcoholic hepatitis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Any variceal bleeding within 12 months of randomisation, assessed through endoscopy for the variceal band ligation (VBL) and through observation for the carvedilol arm at 4 weeks and after 6 and 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Time to first variceal bleed in days from randomisation, assessed through endoscopy for the variceal band ligation (VBL) and through observation for the carvedilol arm at 4 weeks and after 6 and 12 months 2. Mortality at 12 months from randomisation, assessed using medical records and staff notification after 6 and 12 months: 2.1. All-cause mortality 2.2. Liver-related mortality 2.3. Cardiovascular mortality 3. Transplant-free survival at 12 months after randomisation, assessed using medical records and staff notification after 6 and 12 months 4. Adverse events related to treatment up to 12 months after randomisation, assessed using follow-up case report forms (CRFs), medical records and staff notification after 6 and 12 months: 4.1. Dysphagia 4.2. Symptomatic hypotension 4.3. Dyspnoea 4.4. Gastrointestinal upset 5. Other complications of cirrhosis, assessed using follow-up case report forms (CRFs), medical records and staff notification after 6 and 12 months: 5.1. New onset ascites 5.2. New onset encephalopathy 5.3. Spontaneous bacterial peritonitis 5.4. Hepatocellular carcinoma 5.5. Any renal dysfunction 6. Health-related quality of life, assessed using the EQ-5D-5L at the baseline and after 6 and 12 months 7. Use of healthcare resources, cost and cost-effectiveness, based on: 7.1. Cost per variceal bleeding avoided within 12 months of randomisation, assessed using a follow-up CRF 7.2. Cost per Quality-Adjusted Life Year (QALY) estimated using the EQ-5D-5L 7.3. Cost per death avoided at 12 months, assessed using a follow-up CRF 8. Patient preferences, assessed using qualitative interviews that explore patients' experience of and preferences related to treatment (carvedilol or VBL), providing the basis to describe qualitatively patients' experience of the trial interventions. The first interview will be just after randomisation (ideally wuthin 2 weeks) and the second will be 6-12 months after randomisation. 9. Use of alternative therapies, assessed using a fol | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Outcome results
None listed