The ORION-4 trial, which is aiming to find out if a new cholesterol-lowering drug can safely reduce the risk of cardiovascular disease has completed recruitment, with 16,124 participants, including 13,190 in the UK.
We have known for many years that having high levels of low-density lipid (LDL) cholesterol (sometimes called ‘bad cholesterol’) can increase a person’s risk of developing cardiovascular disease. There are treatments available, such as statins, which work very well to lower levels of LDL-cholesterol and reduce the risk of heart attacks and strokes.
The ORION-4 trial is testing a new LDL-cholesterol lowering medicine called inclisiran in men aged at least 40 years and women aged at least 55 years who have previously had a heart attack or stroke, or undergone surgery to unblock or bypass an artery to their legs. These people are at greater risk of having heart and circulatory complications in the future, so could benefit significantly from treatments that lower cholesterol.
Unlike many drugs designed to lower cholesterol levels such as statins, which are taken as a daily tablet, inclisiran is given to patients as an injection under the skin just twice a year. Inclisiran has been approved for use in the UK as a treatment with a well-tolerated safety profile, and is already available to lower cholesterol in some people who have experienced a heart attack or stroke under certain circumstances.
Each participant has been randomly allocated by a computer to receive either inclisiran or a placebo injection. (The placebo injection is just like the inclisiran injection but has no active medicine in it.) To make the results as reliable as possible, neither the doctor nor the participants know whether they are receiving inclisiran or the placebo. The participants have been asked to remain in the trial for around five years and will attend clinic appointments close to their home approximately every six months.
Participants have been recruited in the UK through a collaboration with NHS DigiTrials. Patients who could potentially take part in the study were identified from data about hospital admissions by NHS England. With the right approvals, invitation letters were mailed to them by the University of Oxford, offering a study appointment in their local hospital. This meant that large numbers of potentially eligible patients could be invited and the research staff in the hospitals did not need to spend time searching for patients to invite. A similar process was set up in Wales and Scotland with support from the Health Boards in Wales, Public Health Scotland, and the Health Informatics Centre at the University of Dundee.
Leslie Rhodes, who is taking part in the study in Oxford, said ‘So much medical research depends on volunteers, so taking part in the study seemed an obvious thing to do. And taking part is now so user-friendly, not a difficulty at all. So why not?’
Janet Morgan, another study participant in Cheltenham, added ‘Taking part in the study is just so simple. Even easier than going to the dentist, and much more fun! The study clinic appointments just take 15-20 minutes, and the injections don’t hurt at all!’
Professor Louise Bowman, who is leading the study, said ‘Although having a good diet and taking statins can help lower ‘bad’ cholesterol, sometimes these are not enough to lower a person’s risk of heart disease. We are extremely grateful to the 16,124 people who are helping us to better understand the potential of inclisiran for preventing heart attacks and strokes, which could save many thousands of lives.’
The trial was developed by scientists at Oxford Population Health’s Clinical Trial Service Unit and Epidemiological Studies Unit. The trial is co-sponsored by the University of Oxford and Novartis (the company that produces inclisiran), and is designed and run in collaboration with researchers from the Thrombolysis in Myocardial Infarction (TIMI) Study Group at Brigham and Women’s Hospital in Boston, USA.