Title: Randomised controlled trial of a new relief inhaler in mild asthma
Funder: Department of Health and Social Care

Abstract: Asthma is a common condition affecting approximately 10% of adults in the UK. Many people have relatively “mild” asthma, defined as requiring a reliever (blue) inhaler for breakthrough symptoms with or without, low dose inhaled steroid (preventer) treatment. _x000D_ _x000D_ The main problem in asthma, including “mild” asthma, is inflammation in the airways so the most important treatment is regular inhaled steroids which dampen down this inflammation. Blue, reliever inhalers are used to provide symptom relief but they have no effect on the inflammation and may even make it worse if used regularly without a steroid inhaler. This may explain why increasing use of reliever inhalers and decreasing use of preventer inhalers is associated with asthma deaths. Unfortunately, despite many decades of asthma education, many patients rely on their reliever inhaler at the expense of their preventer inhaler, putting themselves at risk of an asthma attack and even death._x000D_ _x000D_ To help address this problem, The Global Initiative for Asthma (world-wide recommendations for asthma) recently took the bold, but controversial step, of replacing the standard blue, reliever inhaler as the first-choice inhaler to treat symptoms, for all patients with asthma. Instead, they recommended a combination inhaler which contains both a reliever drug and a preventer drug so that patients get a puff of preventer every time they use their reliever. Theoretically, this overcomes the problem of patients not using their preventer regularly and it provides more preventer when asthma control is getting worse (ie more when it is needed)._x000D_ _x000D_ In more severe asthma, the use of a combination inhaler for symptom relief is already known to be better at preventing asthma attacks and hospital admissions than the traditional blue inhaler. More recently some benefit has been shown in “mild” asthma but we believe more evidence is required, especially for patients taking low dose inhaled steroids because, to date, nobody has studied the combination of low dose inhaled steroid with a combination inhaler for symptom relief. There are also no data on how cost effective this new approach is in “mild” asthma compared with the current standard of care. This is particularly important because combination inhalers are considerably more expensive than traditional reliever inhalers. Finally, there is a lack of data on health care professionals and patients views on this fundamental change in asthma care._x000D_ _x000D_ We, therefore, wish to determine the effectiveness of a combination inhaler for symptom relief, instead of the traditional blue inhaler, in patients already on, or starting, a low dose steroid inhaler. We will compare the overall costs and savings made with these two approaches and we will interview a cross-section of health care providers and patients taking part in the study to determine their views on replacing the blue inhaler. _x000D_ _x000D_ Overall the study will require 2300 volunteers with mild asthma across different regions of the UK, particularly focussing on areas where overuse of blue inhalers and asthma attacks are known to be a problem. Volunteers will be divided into two groups to allow a comparison of the new approach with the current standard approach. We have included patients with asthma throughout our plans to ensure they are in-line with patient expectations and we have appointed a patient co-applicant who will join the trial advisory committee.

Lay abstract: Asthma is a common condition affecting approximately 10% of adults in the UK. Many people have relatively “mild” asthma, defined as requiring a short-acting beta-agonist (SABA) for breakthrough symptoms with or without, daily low dose inhaled corticosteroids (ICS). _x000D_ _x000D_ The main problem in asthma is inflammation of the airways, making ICS treatment essential. SABA inhalers are used to provide symptom relief, but they have no effect on airway inflammation and may even make it worse, if used regularly without an ICS. This, combined with poor adherence to ICS inhalers, probably explains why increasing use of SABA and decreasing use of ICS is associated with asthma exacerbations and deaths. _x000D_ _x000D_ To help address this problem, The Global Initiative for Asthma (GINA) recently took the bold, but controversial step, of replacing SABA’s as the first-choice inhaler to treat symptoms for all severities of asthma. Instead, they recommended a combination inhaler which contains both a beta-agonist (usually formoterol) and an ICS so that patients get a puff of ICS every time they use their relief inhaler for symptoms. Theoretically, this overcomes the problem of patients not using their ICS regularly and it provides them with more ICS when asthma control is getting worse. _x000D_ _x000D_ In more severe asthma, the use of ICS/formoterol for symptom relief is already known to be better than SABA at preventing asthma attacks and hospital admissions. More recently some benefit has been shown in mild asthma, but we believe more evidence is required, especially for patients taking low dose ICS because, to date, this has not been studied. There are also no data on how cost effective the combination of ICS/formoterol is in mild asthma compared with the current standard of care. Finally, there is a lack of data on health care professionals and patients' views on this fundamental change in asthma care. _x000D_ _x000D_ We, therefore, wish to determine the clinical benefit and cost effectiveness of ICS/formoterol for symptom relief, instead of SABA, in patients already on, or starting, low dose daily ICS. We will interview a cross-section of health care providers and patients taking part in the study to determine their views on this new approach. _x000D_ _x000D_ Overall, the study will require 2300 volunteers with mild asthma across the UK, specifically targeting those areas known to have high levels of SABA overuse and asthma exacerbations. Participants will be randomised 1:1 to SABA or ICS/formoterol, as required, for symptoms relief with their low dose ICS, as maintenance treatment. To overcome the problems associated with COVID-19 and to keep the study as pragmatic as possible we have limited study visits to baseline, 1 month (remote) and end of study with the primary outcome (severe asthma exacerbations) being recorded from monthly text messages with a check for missing events being captured via a medical notes review at the end of the study. _x000D_ _x000D_ We have brought together a team of clinical trial and asthma experts who have a track record of delivering large trials and we have included patients with asthma throughout our plans to ensure they are in-line with patient expectations. The results will be widely disseminated via national conferences high impact journals, key stakeholders, NHS decision makers and national asthma guidelines. We will inform participants of the trial results and create a video on the trial website explaining the trial results in lay-terms

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: RESPIRATORY