TY - JOUR T1 - 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 JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00271-2021 SP - 00271-2021 AU - Lee Hatter AU - Pepa Bruce AU - Mark Holliday AU - Augustus J Anderson AU - Irene Braithwaite AU - Andrew Corin AU - Allie Eathorne AU - Arthur Grimes AU - Matire Harwood AU - Thomas Hills AU - Ciléin Kearns AU - Kyley Kerse AU - John Martindale AU - Barney Montgomery AU - Lynn Riggs AU - Davitt Sheahan AU - Nick Shortt AU - Katja Zazulia AU - Mark Weatherall AU - David McNamara AU - Catherine A Byrnes AU - Andrew Bush AU - Stuart R Dalziel AU - Richard Beasley Y1 - 2021/01/01 UR - http://openres.ersjournals.com/content/early/2021/06/17/23120541.00271-2021.abstract N2 - 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.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Lee Hatter has nothing to disclose.Conflict of interest: Pepa Bruce has nothing to disclose.Conflict of interest: Mark Holliday has nothing to disclose.Conflict of interest: Augustus John Anderson has nothing to disclose.Conflict of interest: Irene Braithwaite has nothing to disclose.Conflict of interest: Andrew Bush has nothing to disclose.Conflict of interest: Allie Eathorne has nothing to disclose.Conflict of interest: Arthur Grimes has nothing to disclose.Conflict of interest: Matire Harwood has nothing to disclose.Conflict of interest: Thomas Hills reports financial support for the present manuscript from Health Research Council for New Zealand, by way of a research grant.Conflict of interest: Ciléin Kearns has nothing to disclose.Conflict of interest: Kyley Kerse has nothing to disclose.Conflict of interest: John Martindale has nothing to disclose.Conflict of interest: Dr Barney Montgomery has nothing to disclose.Conflict of interest: Lynn Riggs has nothing to disclose.Conflict of interest: Dr Davitt Sheahan has nothing to disclose.Conflict of interest: Nick Shortt reports financial and non-financial support for the present manuscript from HRC (NZ), Cure Kids and AstraZeneca.Conflict of interest: Katja Zazulia has nothing to disclose.Conflict of interest: Mark Weatherall has nothing to disclose.Conflict of interest: David McNamara has nothing to disclose.Conflict of interest: Associate Professor Catherine A Byrnes reports grants from Health Research Council, ‘FluLab’, Curekids and National Health & Medical Research Council, outside the submitted work. Associate Professor Catherine A Byrnes also reports to be an active Editorial Board member for NZ Formulary for Children Member.Conflict of interest: Andrew Bush has nothing to disclose.Conflict of interest: Stuart R Dalziel reports financial and non-financial support for the present manuscript from HRC (NZ), Cure Kids and AstraZeneca.Conflict of interest: Richard Beasley reports financial and non-financial support for the present manuscript from HRC (NZ), Cure Kids and AstraZeneca. Research funding from AstraZeneca and Grenentech, outside the submitted work. Payment or honoraria received from AstraZeneca, Cipla, Avillion and Theravance, outside the submitted work. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for Asthma and Respiratory Foundation (NZ), outside the submitted work. ER -