Plain English Summary
Background and study aims
In patients with chronic liver disease, rebleeding after a first variceal bleed (bleeding from the blood vessels in the oesophagus [food pipe] or stomach) is common, but is reduced by endoscopic therapy (band ligation) of the varices (dilated blood vessels). Initial studies have suggested that propranolol with or without isosorbide mononitrate tablets may be equally effective in reducing rebleeding and are cheaper and easier to take.
Recent data suggests that carvedilol tablets may be the best medical therapy to reduce the risk of variceal bleeding. Therefore our aim was to investigate whether oral carvedilol therapy was superior to standard endoscopic band ligation at preventing rebleeding following a first variceal bleed.
Who can participate?
We aim to recruit 152 patients, male or female, aged between 18 and 75 with a diagnosis of oesophageal variceal bleeding and cirrhosis.
What does the study involve?
Patients who are stable in hospital after a first variceal bleed will be invited to enter the study. Eligible patients who consent will be randomly allocated to receive either oral carvedilol (6.25 mg for one week, then 12.5 mg daily thereafter) or standard endoscopic band ligation of their varices. Patients will be followed up until 6 months after the last patient is allocated.
What are the possible benefits and risks of participating?
There will be no immediate direct benefit to those taking part. However, there should be benefits to future patients because the results of the study are likely to influence how we treat similar patients in the future. The risks of carvedilol therapy are the same as those of any tablet which may reduce blood pressure, including dizziness or fainting.
Where is the study run from?
This multicentre study is being run from Glasgow Royal Infirmary. Patients will be recruited in Scotland, from Glasgow Royal Infirmary (the lead coordinating centre), the Royal Infirmary of Edinburgh, Gartnavel General Hospital Glasgow and the Southern General Hospital Glasgow.
When is the study starting and how long is it expected to run for?
The recruitment started in June 2006 and will run until the estimated number of patients has been recruited, which is expected to be end of 2013.
Who is funding the study?
Greater Glasgow & Clyde Health Board (UK).
Who is the main contact?
Dr Adrian Stanley
adrian.stanley@ggc.scot.nhs.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Adrian Stanley
ORCID ID
Contact details
c/o GI Unit
Glasgow Royal Infrimary
Castle St
Glasgow
G4 OSF
United Kingdom
+44 141 211 4073
adrian.stanley@ggc.scot.nhs.uk
Additional identifiers
EudraCT number
2006-000670-74
ClinicalTrials.gov number
Protocol/serial number
RN03GA006
Study information
Scientific title
Multicentre randomised controlled study comparing carvedilol with endoscopic band ligation in the prevention of variceal rebleeding
Acronym
Study hypothesis
The aim of this study is to investigate whether therapy with oral carvedilol tablets superior to endoscopic variceal band ligation in preventing rebleeding from varices.
Ethics approval
Glasgow Royal Infirmary North Glasgow NHS Trust Ethics Committee, 26/04/2004, ref: 03GA006
Study design
Randomised controlled study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Variceal rebleeding in cirrhotic patients
Intervention
Oral carvedilol tablets versus endoscopic band ligation
Carvedilol is 6.25 mg once daily for one week and if tolerated then 12.5 mg once daily until the study is completed (6 months after the last patient is randomised)
Band ligation is done every 2-3 weeks until eradication then patient is endoscoped 6 monthly, with further bands applied as necessary.
Intervention type
Drug
Phase
Not Applicable
Drug names
Carvedilol
Primary outcome measure
Variceal rebleeding is monitored when it occurs during follow-up. Patients will be followed up until 6 months after the last patient is randomised.
Secondary outcome measures
1. Mortality
2. Any upper gastointestinal bleeding is monitored when it occurs during follow-up
Overall trial start date
06/06/2006
Overall trial end date
31/12/2013
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Male or female aged ≥18 and <75yrs
2. Endoscopic diagnosis of oesophageal variceal bleeding
3. Cirrhosis (based on previous liver biopsy or clinical, biochemical and ultrasonographic findings)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
152
Participant exclusion criteria
1. Age <18 or >75 years
2. Advanced malignancy or another condition associated with a life expectancy of < 6/12 months
3. Previous transjugular intrahepatic portosystemic shunt (TIPS) or porto-caval shunt surgery
4. Portal vein thrombosis
5. Obstructive airways disease
6. Severe peripheral vascular disease
7. Heart block
8. Severe heart failure
9. Pregnancy
10. Type I diabetes mellitus
11. Gastric variceal bleed
12. Treatment with beta blockers or alpha blockers within 4 weeks of index bleed
Recruitment start date
06/06/2006
Recruitment end date
31/12/2013
Locations
Countries of recruitment
United Kingdom
Trial participating centre
c/o GI Unit
Glasgow
G4 OSF
United Kingdom
Sponsor information
Organisation
Greater Glasgow & Clyde (UK)
Sponsor details
R&D Department
38 Church St
Tennant Institute
Glasgow Biomedicine
1st Floor
Western Infirmary
Glasgow
G11 6NT
United Kingdom
+44 141 232 1813
maureen.travers@ggc.scot.nhs.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Greater Glasgow & Clyde Health Board (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2014 results in https://www.ncbi.nlm.nih.gov/pubmed/24953021