START CARE: a protocol for a randomised controlled trial of step-wise budesonide-formoterol reliever-based treatment in children.

Background: Asthma is the most common chronic childhood respiratory condition globally. Inhaled corticosteroid (ICS)-formoterol reliever-based regimens reduce the risk of asthma exacerbations compared with conventional short-acting β ₂ -agonist (SABA) reliever-based regimens in adults and adolescents. The current limited evidence for anti-inflammatory reliever therapy in children means it is unknown whether these findings are also applicable to children. High-quality randomised controlled trials (RCTs) are needed.
Objective: The study aim is to determine the efficacy and safety of budesonide-formoterol reliever alone or maintenance and reliever therapy (MART) compared with standard therapy: budesonide or budesonide-formoterol maintenance, both with terbutaline reliever, in children aged 5 to 11 years with mild, moderate and severe asthma.
Methods: A 52-week, multicentre, open-label, parallel group, phase III, two-sided superiority RCT will recruit 400 children aged 5 to 11 years with asthma. Participants will be randomised 1:1 to either budesonide-formoterol 100/6 µg Turbuhaler reliever alone or MART; or budesonide or budesonide-formoterol Turbuhaler maintenance, with terbutaline Turbuhaler reliever. The primary outcome is moderate and severe asthma exacerbations as rate per participant per year. Secondary outcomes are asthma control, lung function, exhaled nitric oxide and treatment step change. Assessment of Turbuhaler technique and cost-effectiveness analysis are also planned.
Conclusion: This will be the first RCT to compare the efficacy and safety of a step-wise budesonide-formoterol reliever alone or MART regimen with conventional inhaled ICS or ICS-long-acting β-agonist maintenance plus SABA reliever in children. The results will provide a much-needed evidence base for the treatment of asthma in children.
Competing Interests: Conflict of interest: L. Fleming reports consulting fees from AstraZeneca, Sanofi Regeneron and GSK, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events for AstraZeneca, Novartis and Sanofi Regeneron, outside the submitted work. Conflict of interest: C.A. Byrnes reports grants or contracts from the National Health and Medical Research Council Australia, Fisher & Paykel, the Buddle Findlay & Paul Stevenson Memorial Fund and FluLab, outside the submitted work; participation on a Clinical Advisory Panel for Cystic Fibrosis New Zealand and as a Bronchiectasis Foundation Trustee, outside the submitted work; and is a group for Chair, Respiratory Network, Paediatric Society of New Zealand, and a member of the Royal Australasian College of Physicians Paediatric Research Committee, outside the submitted work. Conflict of interest: D. McNamara reports participation on a data safety monitoring board or advisory board for PRECARE study primary outcome arbitration committee, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group for Co-Chair NZ Paediatric Respiratory and Sleep Clinical Network Reference Group, and Member Scientific Advisory Board, Asthma and Respiratory Foundation of NZ, outside the submitted work. Conflict of interest: S.R. Dalziel reports grants or contracts from Cure Kids New Zealand, Health Research Council New Zealand and Starship Foundation, outside the submitted work. Conflict of interest: R. Beasley reports receiving support for the present manuscript from AstraZeneca; grants or contracts from AstraZeneca, Genentech, HRC (NZ) and Cure Kids NZ, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Avillion, Cipla, Teva and CSL Seqirus, outside the submitted work; support for attending meetings and/or travel from AstraZeneca, Avillion, Cipla, Teva and CSL Seqirus, outside the submitted work; NZ asthma guidelines chair, and GOLD board member, disclosures made outside the submitted work; and receipt of equipment, materials, drugs, medical writing, gifts or other services from AstraZeneca, outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose.
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