A randomised controlled trial of alternative treatments toInhibit VEGF in Age-related choroidal Neovascularisation (IVAN)

Wet or neovascular age-related macular degeneration (nAMD) is a condition which causes severe sight loss in older people. This condition is due to a pathological process in which new blood vessels grow into the central region of the retina of the eye, known as choroidal neovascularisation (CNV). These vessels are leaky and lead to the accumulation of fluid between and within the layers of the retina with serious adverse effects on central vision.

Lucentis® is an 'anti-VEGF' drug which is injected monthly into the eye which causes these blood vessels to stop leaking and to shrink. With treatment, eyesight improves in a quarter of affected people and, in the majority (90% or more), eyesight does not deteriorate over two years. These results represent a major improvement over previous treatments. Another anti-VEGF drug, Avastin® (from which Lucentis was derived), may be equally good and is considerably less expensive but its efficacy and safety have only been studied in case series.

The IVAN trial wass a head-to-head comparison of the efficacy and safety of Avastin® and Lucentis®. The IVAN trial studied whether the number of treatments needed can be reduced by comparing monthly anti-VEGF treatment for 2 years with monthly anti-VEGF treatment for 3 months only, with careful monthly review and re-starting treatment if any signs of disease recur.

The study randomised patients to various combinations of active treatment; all patients recruited to the trial received anti-VEGF treatment in one or other combination. Eyesight was assessed at each visit and information collected on quality of life and the costs and burden of illness, which was compared between the different groups after 1 and 2 years follow-up.

Two Year Findings

Tthe two-year findings of the IVAN trial, led by Professor Usha Chakravarthy (Queens University) and co-ordinated by Bristol CTEU, were presented in a planetary session at the Association for Research in Vision and Ophthalmology (ARVO) conference in May 2013. The results show that the two drug treatments Lucentis and Avastin are equally effective in treating neovascular or wet age-related macular degeneration (wet AMD).


Bristol University Press release 

The Lancet- IVAN two year findings 



The Effectiveness of Community versus Hospital Eye Service follow-up for patients with neovascular age-related macular degeneration with quiescent disease: a virtual trial

Wet, or neovascular, age-related macular degeneration (nAMD) is a condition which causes severe sight loss and is the most common cause of blindness in older people in the UK.  nAMD develops when abnormal blood vessels form in the part of the eye responsible for central vision (the field of vision when looking straight ahead).  The current treatment for patients with nAMD is monthly observation and administration of a drug which is designed to block one of the chemicals responsible for the growth of new blood vessels.  The drug is injected into the eye when the disease is active and stopped when the disease process is controlled.

Hospital eye doctors (ophthalmologists) continue to see patients monthly, even when no injections are needed, because there is a very high risk of needing to restart treatment at some point in the future.  This is burdensome for patients and for busy hospital clinics, particularly since the need for monthly treatment diminishes over time. 


The Echoes study aimed to determine whether follow up by optometrists in optician practices in the community is as good as follow-up by opthalmologists.  Rather than carrying out a new trial, eye images (colour fundus and ocular coherence tomography images) collected during a large UK based multicentre clinical trial (the IVAN trial) were used to determine whether optometrists can detect disease activity and make the same decisions about re-treatment as opthalmologists. 

The NIHR have created a summary which can be read here: http://www.nets.nihr.ac.uk/news/all/2016/routine-monitoring-of-eye-condition-effective-in-the-community and the full paper accessed via this link: http://bmjopen.bmj.com/content/6/7/e010685.full


Effectiveness and cost-effectiveness of serum B-type natriuretic peptide (BNP or NT-BNP) testing and monitoring in patients with heart failure (HF) in primary and secondary care

Heart failure happens when the heart becomes damaged, for example after a heart attack, and cannot adequately pump blood around the body.  B-type natriuretic peptide (BNP) is a chemical secreted by the heart in response to injury and its levels in the blood increases in people with heart failure.  Doctors have suggested that measuring BNP in the blood regularly and adjusting heart failure medications to lower BNP levels (BNP-guided treatment) may be better than adjusting medications based on symptoms alone.

Several studies have been conducted in which patients are allocated by chance to receive either BNP-guided treatment or standard treatment without having BNP measured. We combined the “raw” data collected on each participant in these studies in a meta-analysis, which is a statistical technique for combining the findings from independent studies.  We requested the raw data from all investigators who conducted these studies.

We also assembled a representative group of patients with heart failure in the UK and determined whether those who have BNP measured have better outcomes than those who do not. For this we used data that are routinely collected by hospitals and GP practices in the UK.  The results from Monitor will help doctors to decide whether BP-guided treatment should be offered to all patients with heart failure in the UK. 


The paper for the study can be read here: https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/2046-4053-3-41


A multi-centre randomised controlled trial of Transfusion Indication Threshold Reduction on transfusion rates, morbidity and healthcare resource use following cardiac surgery (Titre 2)

Indications for blood transfusion after cardiac surgery are poorly defined. Unnecessary blood transfusions increase healthcare costs both directly, because blood is an increasingly scarce and expensive resource, and indirectly, due to complications associated with transfusion. Transfusion may cause complications by reducing patients' ability to fight off infection and respond to the stress that surgery puts on the body, as well as (rarely) by transmitting viral infections present in donor blood. In the UK, cardiac surgery uses more than 6% of all donor blood (and about 10% of donor blood in the UHBristol, a tertiary cardiac surgery centre). Although the benefits of red cells for managing life-threatening bleeding are clear, the majority of decisions to transfuse after surgery are made on the basis of a patient's haemoglobin (Hb) level (a measure of the ability of the blood to transport oxygen around the body). The level that causes a doctor to transfuse a patient varies widely and randomised trials in non-cardiac surgical fields have shown that lowering the level that 'triggers' transfusion reduces complications as well as the use of blood.

The research was carried out in a number of UK hospitals. Patients whose Hb level dropped below the level at which transfusion is conventionally given were assigned by chance to have decisions made: (a) more or less as they are now, or (b) only when the Hb level drops to a lower, 'restrictive' level. The primary outcome was the number of infectious (sepsis) and ischaemic (stroke, heart attack or kidney failure) complications that occurred during the first 3 months after surgery. 


Liberal or Restrictive Transfusion after Cardiac Surgery - full paper can be accessed here



Coagulation and platelet laboratory testing in cardiac surgery

Blood transfusion is a lifesaving treatment for excessive bleeding that is used commonly in patients having major surgery. However, blood transfusion is also expensive and has harmful effects on the
immune system and circulation of recipients. As a consequence, the need to improve how blood is used was recognised as an NHS strategic priority in 2007. Heart surgery often causes excessive bleeding and accounts for over 6% of all blood transfused in the UK. One important reason for this statistic is that heart surgery patients often have abnormal blood clotting. This can be because of tablet medication for heart disease taken before surgery or as an effect of the techniques used to perform heart surgery.

We will investigate whether it is useful to perform blood tests either just before, or just at the end of heart surgery to identify exactly how the blood clotting system is abnormal in each patient. The results of these tests could potentially lead to recommendations to give specific treatments to patients to improve blood clotting and reduce bleeding and blood transfusion. We will perform this research over 24 months by taking two blood tests from 2400 consecutive patients having heart surgery at the University Hospitals Bristol. The blood will be analysed using specialist blood clotting tests so that we can identify exactly what abnormalities are present. We will test the blood using blood clotting analysers that are designed to be used in the operating theatre to find out how often these analysers correctly identify a clotting abnormalities and what additional test information is required to give the correct diagnosis when they do not. We will also investigate how our laboratory test results relate to the amount of bleeding and other complications in our patients. This information will show us the benefits of performing different kinds of tests so that we can recommend the best tests to perform in future.






During heart surgery, doctors take measurements to make sure that a patient has enough oxygen for their body to function properly. For example, they check the oxygen supply to the whole body by measuring the amount of oxygen in the blood. When these ‘whole bod’ measures of oxygen show that the body is not getting enough oxygen, doctors try to improve the oxygen supply.

During surgery, doctors also monitor the amount of red cells in the patient’s blood (known as the ‘haematocrit’). Red cells are important because they carry oxygen around the body. Doctors try to keep the haematocrit above a set level because it is assumed that, otherwise, the body will not receive enough oxygen. If a patient’s haematocrit falls below the pre-set level, doctors may give the patient a blood transfusion to try to increase the amount of oxygen available to the body.

These practices are not ideal. Sometimes the haematocrit and the oxygen supply to the body can be normal even when oxygen levels in specific organs and tissues are low. Also we know that transfusing blood to keep the haematocrit above a pre-set level does not always increase the oxygen levels in specific body organs unless they are very low to begin with and although blood transfusions may be beneficial, they can cause harm. Doctors therefore want to avoid unnecessary transfusions where possible.

We think that monitoring oxygen levels in specific organs during surgery would be a better way to decide whether a blood transfusion is needed. Developments in technology mean that we can safely measure the oxygen level in the brain during surgery using sensors placed on the forehead. Using this method, we can adjust the oxygen supply and blood transfusion during surgery to the needs of the individual patient, instead of applying the pre-set level to all patients (as we do now). We believe that the brain is the best organ to monitor because it is most sensitive to decreases in oxygen.

The Pasport study investigated whether monitoring the oxygen level in the brain improves the health of patients after the operation and reduces the number of blood transfusions. We compared this new method with the current method of monitoring the haematocrit and oxygen supply to the whole body to decide when to transfuse blood.

The Pasport protocol paper was published in December 2015.