Title: Assessing SYmptom-driven versus Maintenance Preventer Therapy for the Outpatient Management of AsThma In Children (ASYMPTOMATIC)
Funder: Department of Health and Social Care

Abstract: Asthma is the commonest long-term disease in children in the UK. It causes cough and difficulty breathing. This happens because the airways narrow, due to swelling and irritation. These symptoms get worse during asthma attacks. In the UK a child with asthma is admitted to hospital every 20 minutes and 20 children die each year from asthma attacks. In the UK we have some of the worst results for childhood asthma in the world._x000D_ _x000D_ It is crucial that we treat asthma in children properly. The main treatment is a preventer inhaler, containing steroids, which prevents irritation of the airways. For many years we have been advising children with asthma to use their preventer inhaler every day. This reduces symptoms of asthma and prevents attacks. However, new guidelines recommend that taking a preventer inhaler every day might not be required in all children. These changes are based on results of recent studies in adults, and some teenagers, with asthma. In the studies, researchers looked at what happens if people only take their preventer inhaler when they have symptoms of asthma. They compared this to when people take their preventer every day. They found no difference in the risk of having asthma attacks, regardless of whether the preventer inhaler was used every day or just when people had symptoms. They found, however, that overall asthma scores were better in the people who took their preventer inhaler daily. _x000D_ _x000D_ It is difficult to know what to recommend for children aged 6-16 years. Asthma in adults is different from asthma in children._x000D_ _x000D_ Less preventer inhaler may make their asthma symptoms worse, but using them too much can cause unwanted side-effects. We are going to do a trial which will help us learn how best to treat children with mild asthma, who have been recently diagnosed. We want to find out if taking a preventer inhaler only when a child has symptoms is as effective as taking it every day._x000D_ _x000D_ The study will involve around 250 GP practices across the UK. Parents of children with mild asthma at any of these practices will be asked if they would like to take part. If the parents agree, their child will be randomly assigned to one of two different approaches to using the preventer inhaler. They will either take it every day, or only when they have symptoms of asthma. We particularly want to know if this increases the chances of having an asthma attack that needs treatment. We also want to see whether there is a difference between the two approaches in terms of asthma symptoms, hospital admissions, and the child’s overall quality of life._x000D_ _x000D_ To answer our question, we will need a large number of participants (approximately 1800). Roughly 70% of all GP practices in the UK store their information in one large database. We will be able to use this database to identify if participants have had an asthma attack or not. This way we will not require the children to attend extra appointments for the study, which would cause inconvenience for them and their parents._x000D_ _x000D_ It is crucial that the views of children with asthma, and their parents, are incorporated in the study. We are working with a specialist team to ensure this happens. _x000D_ _x000D_ Once we have analysed the results, we will publish them in high profile medical journals. We will also present our research at international conferences. To ensure that children and parents find out about the study as well, we will share our findings on social media, and through the Asthma UK website

Lay abstract: Background: Asthma affects 1.1 million children in the UK. They have cough and difficulty breathing because of airway inflammation. These worsen during acute attacks, which are treated with high dose oral corticosteroids (OCS), and are a frequent cause of hospitalisation. The traditional therapeutic approach is to use maintenance inhaled corticosteroids (ICS) to prevent symptoms and attacks, and short acting beta agonist (SABA) to relieve these. Recent randomised controlled trials (RCTs) in adults and adolescents found that in mild asthma ICS may not be required daily. Recommendations from influential international guidelines are that people with mild asthma should use ICS whenever reliever therapy is needed, but not on asymptomatic days. However, this approach has not been tested in children. _x000D_ _x000D_ Aim: to evaluate whether in children (6 to 16 years old) with mild asthma, symptom-driven use of ICS is non-inferior to maintenance ICS with regards risk of asthma attacks requiring OCS. Secondary aims are to compare the strategies on asthma control, hospitalisation, and health utility. We will conduct a cost-analysis of the approaches. We will conduct a Study Within A Trial (SWAT), evaluating text messages to prompt questionnaire completion._x000D_ _x000D_ Design: Pragmatic open-label RCT, in general practices across the UK who feed data to the Clinical Practice Research Datalink (CPRD). All outcomes will be collected from routinely collected data in the Electronic Health Record (EHR). _x000D_ _x000D_ Interventions: Children will be randomised 1:1 to take either maintenance ICS every day or symptom-driven ICS only on days when SABA is required for 12 months. _x000D_ _x000D_ Eligibility: We will use validated codes to identify eligible children in CPRD, and the GP will contact them to discuss recruitment. We will include children with mild asthma who are prescribed ICS (diagnosed by the GP with or without physiological testing), and exclude those hospitalised in the last 12 months or with significant respiratory comorbidity. _x000D_ _x000D_ Outcomes: Primary outcome (asthma attacks needing OCS) will be identified from prescription records, and through linkage with Hospital Episode Statistic (HES) data. Secondary outcomes at 6 and 12 months, via a web-based portal, will be Asthma Control Test (ACT) scores, adherence (Medication Intake Survey-Asthma, MIS-A), and health utility (CHU9D tool). Hospitalisation and mortality will be identified from linked HES data. _x000D_ _x000D_ Sample size: 1854 children (927 per group) will provide 80% power with a one-sided 2.5% significance level to reject the null hypothesis that the symptom-driven regime is inferior to the maintenance regime. We will involve 250 practices, recruiting for 2.5 years. With a consent rate of 40%, this sample could be achieved if 145 practices recruit on average 12.9 children during the trial. CPRD estimates of number of eligible children show this is feasible. We include a two-stage internal pilot based on site enrolment and recruitment, and recruitment and outcome completion rates, at 6 and 12 months after opening respectively._x000D_ _x000D_ Timeline: Study duration = 4.5 years (6 months set up time, 2.5 years recruitment, 1 year follow up, 6 months final analysis/reporting. _x000D_ _x000D_ Output and dissemination: This trial will inform the management of millions of children with worldwide. We will produce high quality publications, and will share results with the general public in a meaningful way that empowers them to make informed healthcare choices.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: RESPIRATORY