Title: Aspirin after hospitalisation with Pneumonia to prevent cardiovascular Events randomised Controlled Trial (ASPECT)
Funder: Department of Health and Social Care

Abstract: Introduction_x000D_ Pneumonia is an inflammation of one or both lungs, usually caused by infection. Pneumonia is very common with 270,000 patients admitted as an emergency to hospital in England every year. Most people recover completely but some have complications. Two of the most significant complications are heart attack or stroke. _x000D_ Around 1 in 13 patients (8%) who are admitted to hospital with pneumonia have a heart attack or stroke within three months. These events are thought to occur because the infection attacks blood vessels and causes clots, reducing the blood reaching the heart or brain. Patients who have a heart attack or stroke take longer to recover from pneumonia and are more likely to die. Aspirin has been used for decades to reduce the chance of having a heart attack or stroke in patients at high risk of either event. It works quickly with limited side effects in the vast majority of patients. _x000D_ _x000D_ Aims_x000D_ We propose to carry out a study to test whether aspirin reduces the risk of a heart attack or stroke in patients who are admitted to hospital with pneumonia. This study needs to recruit 22,600 patients to answer this question. This is a 4-year study with its findings supporting further recommendations for patients with pneumonia._x000D_ _x000D_ Methods_x000D_ Adults over 50 years of age admitted to hospital with pneumonia will be invited to take part. Those who agree will be split into two groups. Every person joining the study will have an equal chance of being in either group, so both groups will be made up of the same kinds of people. One group will be asked to take one tablet of low dose aspirin each day for 3 months, after taking a higher dose (2 tablets daily) whilst in hospital. The other group will not. In all other respects, both groups will have standard pneumonia treatment. _x000D_ Participants will be followed up after 3 months, without having to do anything. We will assess their recovery, specifically whether they have a heart attack or stroke, or any serious side effects of aspirin. We will do this by reviewing the ‘usual care’ health records of participants held by NHS hospitals. Following up participants like this has been shown to be robust, reduces the burden on participants and makes the research much less expensive. _x000D_ To ensure participants are not getting side effects that would not be picked up in their health records, we will contact 2000 participants recruited early in the trial, this will also be an opportunity to discuss whether they took the medication prescribed. _x000D_ _x000D_ Patient and Public Involvement (PPI)_x000D_ This research question and Plain English Summary has been developed with members of the NBT Infection PPI Group. The use of digital follow-up and not using a placebo (dummy tablets) was developed with input from two patients who suffered heart attacks following pneumonia. A PPI representative from the group is a co-applicant on this application and if funded will sit on the trial management group. _x000D_ _x000D_ Dissemination_x000D_ Members of our PPI group are actively involved and supported in activities relating to dissemination and public engagement. A Plain English Summary of the study and its findings will be written with patients’ input and added to trial website accessible to all participants. We will prepare press releases and communicate the headline findings through official social media channels. We will publish our results in medical journals and ensure they are incorporated into treatment guidelines if appropriate.

Lay abstract: Research question: _x000D_ Does aspirin prescription reduce the risk of Major Adverse Cardiovascular Events (MACE) following emergency hospital admission with community acquired pneumonia? _x000D_ _x000D_ Background:_x000D_ Pneumonia is the commonest cause of unplanned hospital admissions worldwide with an estimated 270,000 emergency admissions to NHS hospitals in England every year. Pneumonia causes a short to medium term increased risk of major adverse cardiovascular events (MACE) such as myocardial infarction (MI) or stroke. Although observational studies exist suggesting a protective role for aspirin in preventing post-pneumonia MACE there have been no adequately powered randomised control trials (RCTs). _x000D_ _x000D_ Aims and objectives:_x000D_ To evaluate the effectiveness of aspirin versus usual standard care in preventing MACE in patients over 50 years old admitted to hospital with community-acquired pneumonia._x000D_ The primary outcome is to estimate the difference between randomised groups in MACE within 90 days of randomisation. Secondary outcomes include the difference in all-cause mortality, cardiovascular mortality and major bleeding events up to 90 days._x000D_ _x000D_ Methods:_x000D_ Multi-centre, open-label, parallel group RCT in 22,600 patients hospitalised with pneumonia, with internal pilot and efficient remote outcome measurement. Participants will be randomised to receive oral aspirin as 150mg once daily for 7 days (or until hospital discharge if sooner) followed by 75mg once daily up to 90 days. _x000D_ Follow-up will be facilitated by the remote collection of all outcome data from routine data sources: Hospital Episode Statistics Admitted Patient Care (HES-APC) and Office for National Statistics (ONS) mortality register, as opposed to additional follow-up visits. _x000D_ During the pilot phase of the trial the first 2000 participants will be contacted to assess adverse events which did not lead to hospitalisation and concordance with prescribed medication._x000D_ _x000D_ Timelines for delivery: _x000D_ Total duration 48 months (m), comprising: set up (8m), internal pilot (12m), main trial recruitment (18m), additional follow-up (4m), analysis and reporting (6m). The pilot phase will conclude after the first 12 months recruitment (22 months after contract start) with progression criteria focused on recruitment, safety and MACE event rates. _x000D_ _x000D_ Anticipated impact and dissemination: _x000D_ Around 19,000 fatal and non-fatal MACE occur up to 90 days after admission with pneumonia in English hospitals annually, causing significant long-term morbidity and excess mortality. The high incidence of pneumonia means that there would be about 2,800-3,800 fewer MACE per year if aspirin were to reduce the risk by 15-20% (in England alone). Combined with the cost-effectiveness of aspirin the potential impact of this trial on health policy is very large. _x000D_ We will disseminate trial results on a dedicated trial webpage which will also be updated on progress and recruitment throughout the trial to inform participants and stakeholders. We will prepare press releases and communicate headline findings through social media channels. We will publish our results in medical journals and ensure they are rapidly incorporated into treatment guidelines, if appropriate, using established links with acute care, respiratory and primary care organisations.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR;INFECTION