Participant meetings

So far, the only notable side effects observed in earlier, smaller trials are mild injection site reactions, which occur in small numbers of people and tend to resolve quickly. The ORION-4 trial is designed to detect rare or long-term side effects that may not have been seen in these earlier studies. The trial is monitored regularly by an independent committee of experts who would advise the coordinating team if any important safety concerns emerged in the trial data.

Earlier trials have shown no concerning effects on liver function blood tests, and regular monitoring has not indicated any liver-related safety issues.

Research indicates that very low cholesterol levels do not appear to negatively impact brain health, and the benefits of lowering cholesterol for heart disease and stroke prevention significantly outweigh any potential risks.

Yes, if the results show a benefit in reducing vascular events, it may be used in both populations.

The ORION-4 trial is assessing the effects of inclisiran on heart disease and strokes, as well as a wide range of other medical conditions, in order to provide a complete picture of the drug’s potential benefits and risks.

The placebo is used to provide a fair comparison, ensuring that any benefits or side effects can be accurately attributed to inclisiran.

Yes, current medical advice suggests that inclisiran is most effective when taken alongside statins and other heart-protective therapies, like blood pressure medications and aspirin.

Some studies of intensive cholesterol-lowering treatments suggest that the build-up of plaque might be partly reversible, although it does not seem to be completely removed. However, cholesterol-lowering drugs like statins and potentially inclisiran can significantly slow the progression of plaque and stabilise it, reducing the risk of heart attacks and strokes.

Some tablets that target the PCSK9 protein in the blood are currently in development. However, these work in a different way to inclisiran. Currently, an oral form of inclisiran is not available.

No, the current aim is to complement statin therapy, not replace it. Statins are very effective and inexpensive, and inclisiran is intended to be an additional option for those who need further cholesterol reduction.

At the end of the study, all participants will stop receiving the study drug (whether active or placebo). Once the trial results are available, we will write to you with a summary of the results so that you can discuss your future cholesterol treatment with your healthcare provider.

We do not plan to routinely inform all study participants whether they were on the active drug or the placebo. We will write to you and your GP with a summary of the trial results as soon as they are publicly available so that you can discuss with your GP what you should be taking in the future, based on the results of the study. However, if you want to know if you received the active drug or the placebo, you will be able to contact the Oxford Coordinating Centre after the end of the study, once the results have been fully analysed, to request this information.

The trial team at Oxford does not control the availability of the drug in routine care. However, the findings from this study will provide important information for the NHS, and local and national policymakers, to help decide how widely this drug should be made available. If the results of ORION-4 show that inclisiran helps to protect against heart attacks and strokes, then we hope that it will become widely available for patients.

The ORION-4 trial plans to conduct long-term follow-up using secure electronic NHS records to track the health of study participants over many years, because long-term effects are a critical part of understanding the full benefits and risks of inclisiran. However, there will be no ongoing requirement for participants to attend clinic visits.

The trial team can work with you to adjust the timing of your clinic visit and dose of study treatment to fit with any other medical or other commitments.

To preserve the study's integrity, the ORION-4 researchers do not have access to cholesterol levels measured on your blood samples during the study. If you need to have your cholesterol measured, your own doctors can arrange this as required.

The COVID-19 pandemic caused significant delays as NHS hospitals were focused on managing the crisis, and this paused recruitment temporarily.

You can withdraw at any time, but continuing in the study (even if you are no longer receiving the injections) provides valuable data for the study.

While most medications are safe to take, some other cholesterol-lowering drugs, like evolocumab (Repatha®) and alirocumab (Praluent®), should not be taken at the same time because they target the same pathway as inclisiran.

Inclisiran works by targeting a specific protein in the liver, called PCSK9. By reducing the production of this protein, the liver is able to remove more of the bad (LDL) cholesterol from the blood. This helps lower overall cholesterol levels over time.

Treatment for the study is provided by Novartis, the pharmaceutical company that produces inclisiran, which also helps with the costs of running the study, by a grant given to the University of Oxford. However, the trial is coordinated by Oxford University’s Clinical Trial Service Unit (CTSU) in collaboration with investigators at the TIMI Study Group at Harvard University (USA), ensuring independent oversight and rigorous scientific standards.

Unfortunately, some insurers may increase premiums or deny travel insurance cover based on clinical trial participation, though this practice is strongly discouraged by authorities. The trial team can offer support in addressing these issues.

The injection must be administered by a healthcare professional. It is not currently licensed for self-injection.