Assessing SYmptom-driven versus Maintenance Preventer Therapy for the Outpatient Management of AsThma In Children (ASYMPTOMATIC)

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.

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.

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).

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.

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.

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.

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.

Timeline: Study duration = 4.5-years (6 months set up time, 2.5-years recruitment, 1-year follow up, 6 months final analysis/reporting.

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.