The Children's Anti-inflammatory REliever (CARE) study: a protocol for a randomised controlled trial of budesonide-formoterol as sole reliever therapy in children with mild asthma

Background Asthma is the most common chronic disease in children, many of whom are managed solely with a short-acting β2-agonist (SABA). In adults, the evidence that budesonide-formoterol as sole reliever therapy markedly reduces the risk of severe exacerbations compared with SABA alone has contributed to the Global Initiative for Asthma recommending against SABA monotherapy in this population. The lack of current evidence in children means it is unknown whether these findings are also relevant to this demographic. High-quality randomised controlled trials (RCTs) are needed. Objective To determine the efficacy and safety of as-needed budesonide-formoterol therapy compared with as-needed salbutamol in children aged five to 15 years with mild asthma, who only use a SABA. Methods A 52-week, open-label, parallel group, phase III, RCT will recruit 380 children aged five to 15 years with mild asthma (ACTRN12620001091998). Participants will be randomised 1:1 to either budesonide-formoterol (Symbicort Rapihaler®) 50/3mcg, two actuations as needed or salbutamol (Ventolin®) 100mcg, two actuations as needed. The primary outcome is asthma attacks as rate per participant per year. Secondary outcomes assess asthma control, lung function, exhaled nitric oxide, and treatment step change. A cost-effectiveness analysis is also planned. Conclusion This is the first RCT to assess the safety and efficacy of as-needed budesonide-formoterol in children with mild asthma. The results will provide a much-needed evidence base for the treatment of mild asthma in children.