An introduction to Research | Current research funded by CLDF | Controlled trial of variceal band ligation

Controlled trial of variceal band ligation

A multicentre randomised controlled trial of variceal band ligation for primary prophylaxis of oesophageal variceal bleeding in childhood portal hypertension – a feasibility study

Dr PJ McKiernan, Liver Unit, Birmingham Children’s Hospital

Bleeding from oesophageal varices is the commonest cause of severe gut bleeding in childhood.  Bleeding occurs in approximately 40% of children with varices. In adults primary prophylactic (i.e. before bleeding has occurred) treatment for variceal haemorrhage is standard. 

Two types of treatment are established in adults; beta-blockers and variceal band ligation.  Beta blockade is not well tolerated and studies have shown ligation to be a more effective option.

 There is no prospective data on primary prophylaxis in children. Because of differing pathology and physiology in children, observations from adult practice cannot be directly extrapolated to children.  Beta blockers are not well tolerated in children and appear ineffective. Variceal band ligation has been widely used for secondary prophylaxis of variceal haemorrhage in children who have already bled. In this setting, it has proven to be effective and safe.  This suggests that variceal ligation should be evaluated to prevent first oesophageal variceal bleeding in children with portal hypertension.

Because so little is known in this area it will be necessary to carry out a feasibility study first. This will aim to see whether enough children with varices would be suitable to join the study and how many would agree.

Budget:

	Year I	Year II	Total
a) Staff	£39,731	£21,384	£61,115
c) Consumables	£7,200	£3,600	£10,800
d) Publicity and dissemination (production of information materials, project reports etc)
e) Training for staff	£1,000	£500
f) Research supervision
g) Travel and subsistence	£5,000	£2,500	£7,500
h) Recruitment Costs	£1,500
i) Data analysis and computing costs	£500	£341	£841
TOTAL COSTS	£54,931	£28,325	£83,256

Project: April 2007 for 18 months.

Further information on research study to prevent variceal bleeding in children:

Variceal bleeding is the most feared complication of portal hypertension.   We are delighted that the Children’s Liver Disease Foundation has agreed to fund a pilot research study to see whether it is possible to prevent variceal bleeding in children.

Portal hypertension is abnormally high blood pressure in the circulation from the gut and spleen to the liver.   Portal hypertension occurs when blood cannot flow easily through the liver, either because the liver is hard and stiff due to liver disease or because the portal vein is blocked.   As a result of portal hypertension blood from the gut and spleen tends to find new ways to return to the heart.   This can cause varicose veins to develop at the bottom end of the gullet.    Unfortunately these are thin-walled and are at risk of bursting, causing bleeding.    Variceal bleeding is the commonest cause of severe bleeding from the gut in children. It most commonly occurs as vomiting blood (haematemesis) but blood can appear in the stool where it may be black or tar like in colour (melaena).

Variceal bleeding is a medical emergency and children should be brought to hospital immediately.    There they will be stabilised, given drug treatment and arrangements made for an endoscopy.  Usually the varicose veins are treated at endoscopy by a technique called banding.    This is carried out under anaesthetic and rubber bands are placed around the varicose veins.   This is very effective at stopping bleeding quickly. By repeating this we can prevent re-bleeding.

Can we prevent bleeding in the first place?
This is what this study is setting out to find.  In adults with oesophageal varices it is possible to prevent bleeding by either drug treatment or by using banding before bleeding has occurred, i.e. so-called primary prophylaxis.  This progress was made as a result of randomised controlled trials carried out in adults with liver disease.

In children the situation is less clear.    Unfortunately the drugs that work in adults don’t seem to be as effective in children.  We know that banding is very safe and effective in children but because we don’t know how many children will bleed anyway it is not clear whether we should do banding on all children before bleeding or whether we should wait until they bleed.

When we don’t know the answer to such a question the only solution is a randomised trial. 

Who can take part?

Children with portal hypertension who have large oesophageal varices.

What will they have to do?

If they and their family agree, they will be randomised into two groups.   The first group will receive banding and will be followed up with further endoscopy until all the varicose veins are gone.   The second group will receive no banding and will be followed up as normal.  All the children will be followed up for two years.    During, and at the end of the study, we will compare the amount of bleeding between the two groups.   Taking part is of course entirely voluntary.  Children and families who do take part in this study can change their mind at any time and will be able to withdraw.  This will not affect their care in any way.

Where is the research being carried out?

This is a multi-centre study which is being carried out in Birmingham Children’s Hospital, King’s College Hospital and St. James’s Hospital, Leeds.  

How can I find out any further information:

You may want to mention this at your next out patient appointment or alternatively contact any of the doctors listed below who will be happy to provide further information.

Dr. Patrick J. McKiernan
Consultant Paediatric Hepatologist

Contact information:

Birmingham Children’s Hospital: 0121 333 8254
Dr. Patrick McKiernan   
Dr. Ulrich Baumann    

King’s College Hospital: 0207 3299 3214
Mr. Mark Davenport   
Professor Anil Dhawan 

St. James’s Hospital, Leeds: 0113 206 6880 
Dr. Suzanne Davison    
Dr. Patricia McClean