Randomised controlled trial of a new relief inhaler in mild asthma

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).

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.

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.

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.

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.

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.

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