A novel reliever strategy for children with asthma: CARE-UK: Children’s Anti-Inflammatory Reliever Study

Research question In children aged 4 to 11 years with asthma, is a combination budesonide-formoterol reliever inhaler either used alone or as both maintenance and reliever treatment, more effective at preventing asthma attacks than a traditional short acting beta agonist inhaler, either used alone or in combination with the child’s usual asthma treatment? Background Current UK guidelines recommend that children aged 4 to 11 years with asthma should receive short acting beta agonists (SABA) for relief of symptoms. However, this treatment does not address the underlying cause, i.e., airway inflammation. Although regular inhaled corticosteroids (ICS) are the first line treatment for airway inflammation people with asthma often prefer SABAs as they offer rapid relief of symptoms. Over-reliance on SABAs and SABA only treatment leave patients at risk of ongoing symptoms and asthma attacks. The Global Initiative for Asthma recommends that all people with asthma =12 years use a reliever inhaler containing a combination of ICS and a fast-acting long-acting beta agonist, formoterol. This approach results in simultaneous treatment of airway inflammation and bronchoconstriction, the predominant pathophysiological features of asthma. The combination ICS-formoterol reliever inhaler can be used in two ways: i. Taken as needed for symptom relief, without maintenance therapy ii. Taken regularly as part of daily maintenance treatment and as needed for symptom relief (Maintenance and Reliever Treatment (MART)). Good evidence exists for those =12 years but there is a paucity of data for younger children. Further research is urgently needed to bring the strength of evidence and available treatment options for children on a par with adults and adolescents. Aims and objectives The aim is to determine the clinical effectiveness, safety and cost-effectiveness of ICS-formoterol reliever therapy either used alone for symptom relief, or as part of MART, compared with SABA reliever therapy either used as monotherapy or with the child’s usual maintenance treatment in children with asthma aged 4 to 11 years. The objectives are: 1. To recruit 1,352 children from primary and secondary care with a range of asthma severities 2. To randomise children to the intervention arm (ICS-formoterol as reliever treatment, either alone or as part of MART) or the control arm: standard care (SABA as a reliever inhaler either as monotherapy or with maintenance treatment (ICS or ICS-LABA in keeping with standard care 3. To review children 4 monthly for 1 year and collect data on severe exacerbations (courses of oral corticosteroids) 4. To collect data on secondary outcomes including those related to asthma control, healthcare costs and safety Methods A 52-week multi-centre, parallel group, open label, pragmatic, 2-arm randomised controlled trial. Timelines for delivery The total study duration will be 45 months. Recruitment will take place over 18 months and all participants will be followed up for 12 months. Anticipated impact and dissemination The results of this study will lead to a paradigm shift in National and International clinical guidelines for children with asthma age 4 to 11 years. The results will be disseminated through a range of media to ensure comprehensive stakeholder engagement.