CALIBRE
Research type
Research Study
Full title
CArvediloL versus variceal Band ligation in primary pREvention of variceal bleeding in liver cirrhosis
IRAS ID
248487
Contact name
Dhiraj Tripathi
Contact email
Eudract number
2018-002488-24
Duration of Study in the UK
5 years, 6 months, 31 days
Research summary
Research Summary:
Individuals with liver cirrhosis (scarring of the liver) can develop enlargement of veins in the gullet (food pipe) known as ‘oesophageal varices’. Patients with medium to large oesophageal varices have a 1 in 3 chance of these veins bleeding. In severe cases this could result in death. It is therefore important to lower the risk of this bleeding. At present all patients with medium to large oesophageal varices are offered one of two treatments to lower the risk of bleeding:
Variceal banding
A flexible tube (endoscope) with a miniature video camera and carrying a rubber ring is passed through the mouth to the gullet. An enlarged vein can be tied off with the rubber ring. Several (sometimes up to five) endoscopy sessions at approximately monthly intervals will be required to treat all of the varices. Subsequently, regular checks will be carried out at three, six then 12 months, then annually thereafter.
Beta-blocker drugs
Beta-blockers slow down the heart rate and lower blood pressure. These drugs are either carvedilol, propranolol. Carvedilol is used to treat high blood pressure and some forms of heart disease. Research studies have shown carvedilol to be also very effective and better than propranolol at lowering the pressure in varices in the gullet (the lower the pressure, the lower the risk of bleeding). Patients tolerating beta-blocker tablets will not require any more routine endoscopies to check on their varices.Some research studies suggest that banding may be more effective than beta-blockers in lowering the risk of variceal bleeding, but other studies suggest that this is not the case. However, all of these studies have been small and we still don’t know what treatment is best. CALIBRE aims to compare carvedilol with banding in people with cirrhosis who have medium to large varices that have never bled.
Lay Summary of Results:
A Multicentre Randomised Controlled Trial of Carvedilol Versus Variceal Band Ligation in Primary Prevention of Variceal Bleeding in Liver Cirrhosis (CALIBRE Trial) This trial was sponsored by The University of Birmingham.
The trial was funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme. 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.What was the question?
People with liver cirrhosis (scarring of the liver) can develop enlargement of veins in the gullet (food pipe) known as ‘oesophageal varices’, which can bleed, resulting in a medical emergency. Beta-blocker medicines, such as carvedilol, lower the pressure in the varices to reduce bleeding risk. Banding involves passing a flexible tube (endoscope) with a miniature video camera and carrying a rubber ring through the mouth to the gullet to tie off the varices. It is not clear which treatment offers the best protection against variceal bleeding. The CALIBRE trial aimed to compare carvedilol versus banding in preventing the first variceal bleed in patients with cirrhosis and medium to large oesophageal varices that have not bled.What did we do?
We conducted a clinical trial recruiting participants from 52 hospitals in the UK. Two hundred sixty-five participants were randomly selected to receive carvedilol or banding and followed up for up to one year. We recorded variceal bleeding and other secondary outcomes, such as other complications of cirrhosis, quality of life, cost-effectiveness, and adverse events. A smaller study was also performed to understand the acceptability of the treatments and patient and clinician preferences.What did we find?
Although the trial was stopped early, mainly due to the impact of COVID-19, there was no difference in the variceal bleeding rate at one year in carvedilol, which was 3.7% versus 7.6% in banding. There was no difference in the secondary outcomes, and carvedilol was cheaper and potentially cost-effective. There were no safety concerns. Participants did not express a preference for either treatment, while clinicians preferred carvedilol.What does this mean?
Carvedilol and banding did not differ in preventing variceal bleeding. Since carvedilol has no untoward safety concerns and is well tolerated, cost-saving, and potentially cost-effective, it is the preferred first-line treatment option.REC name
North East - York Research Ethics Committee
REC reference
18/NE/0296
Date of REC Opinion
19 Oct 2018
REC opinion
Further Information Favourable Opinion