Beta-blockers for Oesophageal Varices

Phase

Condition

Varicose Veins

Occlusions

Hepatic Fibrosis

Treatment

N/A

Clinical Study ID

NCT03776955

125861

Ages > 18
All Genders

Study Summary

To determine if carvedilol reduces the rate of variceal haemorrhage in patients with cirrhosis and small oesophageal varices

Eligibility Criteria

Inclusion

Inclusion Criteria:

Age >18 years
Cirrhosis and portal hypertension, defined by any 2 of the following: A) Characteristic clinical examination findings; one or more of i) liver functiontests ii) haematological panel iii) coagulation profile abnormalities B)Characteristic radiological findings; one or more of i) heterogeneous, small liverwith irregular contour ii) splenomegaly iii) ascites iv) varices v) recanalizedumbilical vein C) Fibrosis score > stage 4 on liver biopsy D) FibroScan liverstiffness measurement >15 kilo Pascal without other explanation
Small oesophageal varices diagnosed within the last 3 months,- defined as <5 mm indiameter or varices which completely disappear on moderate insufflation atgastroscopy.
Not received a beta-blocker in the last week
Capacity to provide informed consent

Exclusion

Exclusion Criteria:

Non-cirrhotic portal hypertension
Medium/large oesophageal varices (current or history of), defined as >5 mm in diameter
Isolated gastric, duodenal, rectal varices with or without evidence of recent bleeding
Previous variceal haemorrhage
Red signs accompanying varices at endoscopy
Known intolerance to beta blockers
Contraindication to beta blocker use i) Heart rate <50 bpm ii) Known 2nd degree orhigher heart block iii) Sick sinus syndrome iv) Systolic blood pressure <85 mm Hg v)Chronic airways obstruction (asthma/COPD) vi) Floppy Iris Syndrome vii) CYP2D6 PoorMetaboliser viii) History of cardiogenic shock ix) History of severe hypersensitivityreaction to beta-blockers x) Untreated phaeochromocytoma xi) Severe peripheralvascular disease xii) Prinzmetal angina xiii) New York Heart Association IV heartfailure
Unable to provide informed consent
Child Pugh C cirrhosis
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
Women of child bearing potential not willing to use adequate contraception during theprotocol of IMP dosing
Patients who have been on a CTIMP within the previous 3 months

Study Design

June 17, 2019

December 31, 2024

Study Description

Cirrhosis or liver scarring is an important problem in healthcare in the United Kingdom. 60,000 patients are living with this disease and about 11,000 people every year will die because of it. There are several ways in which patients with this severe form of liver disease become unwell or die and bleeding from the oesophagus or stomach is one. Cirrhosis causes pressure changes inside the abdomen and swelling of veins in the oesophagus (called "varices") which can bleed catastrophically.

The investigators know that when varices are large, treatment can be initiated with medication called beta-blockers to reduce the pressure in the varices. If the varices are small, the medical community is not sure if treatment with beta-blockers will work. This study aims to address this uncertainty.

Patients who are recruited to the study with small varices will be randomised to either beta-blockers or a placebo. Research sites will observe patients closely for 3 years for bleeding from their varices or other complications of cirrhosis or side effects of taking medication. This is the amount of time needed to observe for bleeding when the varices are small. Research sites will review the patients every 6 months including assessing the varices by a camera test called an endoscopy at the beginning and each year until the study is finished.

During the study, patients will be involved with the conduct and management of the research. Patient will also be notified on the trial results at the end of the study. The barriers and facilitators in adjusting the dose of the tablets to optimise treatment effects primary care will be along with patients' views on taking part in the trial, and whether the side effects justify the potential benefits of reducing the risk of bleeding. The investigators estimate this risk could be reduced from 20% of patients having significant bleeding to 10% over 3 years.

The investigators will measure the impact of beta-blockers on the overall costs to the National Health Service (NHS) of caring for people with cirrhosis during the trial, and will also assess the impact of treatment on both mortality and quality of life using a combined measure, the Quality Adjusted Life-Year (QALY). The investigators will use a mathematical prediction model to estimate the impact of treatment on costs, mortality and quality of life over a patient's lifetime and will assess whether any increased costs are justified by better outcomes for patients and represent good value for money for the NHS budget.

Finally, the results of the study will be published in the medical literature and discuss the findings at medical conferences, patient groups and with charities involved in helping patients with cirrhosis such as the British Liver Trust.

Connect with a study center

Royal Victoria Hospital
Belfast, Northern Ireland BT12 6BA
United Kingdom
Site Not Available
Queen Elizabeth Hospital
Birmingham, B15 2TT
United Kingdom
Site Not Available
King's College Hosptial NHS Foundation Trust (Denmark Hill)
London,
United Kingdom
Active - Recruiting
Royal London Hospital (Barts)
London, E1 1FR
United Kingdom
Site Not Available

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