WILLOW TREE
Research type
Research Study
Full title
The impact of aspirin dose modification on the innate immune response - WILL lOWer dose aspirin Therapy ReducE the response to Endotoxin? – (WILLOW TREE)
IRAS ID
254420
Contact name
Robert Storey
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS Foundation Trust
Eudract number
2018-004285-34
Duration of Study in the UK
2 years, 1 months, 27 days
Research summary
Research Summary
Heart attacks are usually caused by blood clots blocking one of the blood vessels supplying the heart, depriving the heart muscle of blood. Platelets are the main type of blood cell causing clotting and we typically give a combination of two ‘anti-platelet’ drugs, aspirin and ticagrelor, to treat this. However, aspirin and ticagrelor have effects not just on the platelets but also on the immune system. On the one hand, aspirin is thought to increase the release of certain inflammatory factors that may be harmful in the long term in heart disease, whereas we previously showed that ticagrelor reduces the release of the same factors. We have been investigating the effects of different doses of aspirin in heart attack patients when taken alongside ticagrelor, and have found that a new, lower dose of aspirin given twice daily, rather than the usual standard dose once daily, reduces the tendency to bleed whilst on treatment, and also appears to reduce the amount of inflammation compared to standard doses. We want to study this further and so have developed this study.
During the two periods of the study, we want to give healthy volunteers combinations of these medications and then stimulate their immune system, in order to see if the medications affect the immune response. The study will involve a period of medication for 10 days followed by a day in hospital stimulating the immune system with an injection into the bloodstream of a substance known as endotoxin, which causes temporary flu-like symptoms, followed by blood and urine tests. We will then repeat the process, after a minimum of five weeks, taking a different medication combination and having a further endotoxin injection. We will also keep in contact by telephone until 2 weeks after the end of the medication to ensure participants remain well.
Lay summary of study results:
Aspirin and ticagrelor are standard treatments for acute coronary syndromes such as heart attacks and unstable angina, where blood supply to the heart gets blocked by blood clots which reduces its ability to pump blood around the body. Platelets are the main type of blood cell causing clotting and patients are normally given a combination of these two ‘anti-platelet’ drugs. They are known to increase bleeding risk in patients but can also reduce inflammation. While often given together, altering the dosing schedule of these medications, such as giving them individually as monotherapy can reduce the bleeding risk. Reduction in inflammation can have a beneficial effect on patients with heart disease.
Healthy volunteers were randomly allocated to one of 8 treatment strategies of differing doses of aspirin/ ticagrelor or no drug and had blood samples taken to look at platelet aggregation and inflammation. The bleeding time test measured how long it took for clots to form.
The results showed that those not receiving aspirin who received a dose of ticagrelor had lower levels of inflammation than those who did not receive ticagrelor. This effect was removed in patients who were receiving aspirin.
In participants receiving aspirin, the bleeding time test took significantly longer in those receiving the higher doses compared to baseline.
In conclusion, lower doses of aspirin (e.g. 20mg twice daily) may offer improved bleeding risk compared to the higher doses. Ticagrelor monotherapy could offer a more beneficial effect on inflammation with a reduced bleeding risk than when given alongside aspirin.REC name
East of England - Cambridge East Research Ethics Committee
REC reference
18/EE/0401
Date of REC Opinion
27 Dec 2018
REC opinion
Further Information Favourable Opinion