Treatment guided by fractional exhaled nitric oxide in addition to standard care in 6- to 15-year-olds with asthma: the RAACENO RCT

Autor:	Turner S; Royal Aberdeen Children’s Hospital, University of Aberdeen, Aberdeen, UK, Cotton S; Health Services Research Unit, University of Aberdeen, Aberdeen, UK, Wood J; Health Services Research Unit, University of Aberdeen, Aberdeen, UK, Bell V; Health Services Research Unit, University of Aberdeen, Aberdeen, UK, Raja EA; Medical Statistics Team, University of Aberdeen, Aberdeen, UK, Scott NW; Medical Statistics Team, University of Aberdeen, Aberdeen, UK, Morgan H; Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK, Lawrie L; Health Services Research Unit, University of Aberdeen, Aberdeen, UK, Emele D; Health Services Research Unit, University of Aberdeen, Aberdeen, UK, Kennedy C; Health Economics Research Unit, University of Aberdeen, Aberdeen, UK, Scotland G; Health Economics Research Unit, University of Aberdeen, Aberdeen, UK, Fielding S; Medical Statistics Team, University of Aberdeen, Aberdeen, UK, MacLennan G; Health Services Research Unit, University of Aberdeen, Aberdeen, UK, Norrie J; Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh, UK, Forrest M; Health Services Research Unit, University of Aberdeen, Aberdeen, UK, Gaillard E; Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester, UK, de Jongeste J; Erasmus University Medical Centre, Rotterdam, the Netherlands, Pijnenburg M; Erasmus University Medical Centre, Rotterdam, the Netherlands, Thomas M; Primary Care and Population Sciences, University of Southampton, Southampton, UK, Price D; Observational and Pragmatic Research Institute, Singapore; Centre of Academic Primary Care, University of Aberdeen, Aberdeen, UK
Jazyk:	angličtina
Zdroj:	2022 May.
DOI:	10.3310/AWOI5587
Abstrakt:	Background: The role of fractional exhaled nitric oxide in guiding asthma treatment in children is uncertain. Objective: To compare treatment guided by both fractional exhaled nitric oxide and symptoms (intervention) with treatment guided by symptoms alone (standard care) in children with asthma who are at risk of an asthma exacerbation, in terms of the number of asthma exacerbations over 12 months. Design: This was a pragmatic, multicentre, randomised controlled trial with embedded cost-effectiveness and qualitative process evaluations. Randomisation (1 : 1) was carried out using a remote web-based system and was minimised on recruitment centre, age, sex and British Thoracic Society treatment step. Clinical teams and participants were not blind to treatment allocation. Setting: The trial took place in 35 hospitals and seven primary care practices in the UK. Participants: Children aged 6–15 years with a diagnosis of asthma who were currently prescribed inhaled corticosteroids and who had one or more parent-/patient-reported asthma exacerbation treated with oral corticosteroids in the 12 months prior to recruitment. Interventions: Asthma treatment guided by symptoms alone (standard care) and asthma treatment guided by symptoms plus fractional exhaled nitric oxide (intervention). Treatment recommendations in both groups were protocolised within a web-based algorithm, incorporating inhaled corticosteroid adherence (objectively measured using an electronic logging device) and current treatment. Main Outcome Measures: The primary outcome measure was asthma exacerbations treated with oral corticosteroids in the year post randomisation. Secondary outcomes included time to first exacerbation, number of exacerbations, lung function, fractional exhaled nitric oxide, daily dose of inhaled corticosteroid, asthma control and quality of life. Results: In total, 509 eligible participants were recruited and the primary outcome was available for 506 participants. The primary outcome occurred in 123 out of 255 (48.2%) participants in the intervention group and 129 out of 251 (51.4%) participants in the standard-care group (adjusted odds ratio 0.88, 95% confidence interval 0.61 to 1.27). There was algorithm non-compliance on 21% of assessments. Per-protocol and complier-average causal effect analysis did not change the interpretation. This non-statistically significant estimate was consistent across predefined subgroups. There were no differences between the groups in secondary outcomes. There were no serious adverse events or deaths. No meaningful differences in health service costs, direct patient costs or indirect costs to society were identified between the groups. The economic evaluation does not provide evidence to support the cost-effectiveness of the intervention. In the qualitative process evaluation, 15 trial staff and six families were interviewed. Overall, their experiences were positive. The intervention was broadly acceptable, with caveats around clinicians using the algorithm recommendation as a guide and wariness around extreme step ups/downs in treatment in the light of contextual factors not being taken into account by the algorithm. Limitations: Potential limitations included the choice of cut-off point to define uncontrolled asthma and the change in fractional exhaled nitric oxide to trigger a change in treatment. Furthermore, the treatment decisions in the two groups may not have been sufficiently different to create a difference in outcomes. Conclusions: The RAACENO (Reducing Asthma Attacks in Children using Exhaled Nitric Oxide) trial findings do not support the routine use of fractional exhaled nitric oxide measurements as part of asthma management in a secondary care setting. The potential for other objective markers to guide asthma management in children needs to be evaluated. Trial Registration: This trial was registered as ISRCTN67875351. Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health and Care Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation ; Vol. 9, No. 4. See the NIHR Journals Library website for further project information. (Copyright © 2022 Turner et al. This work was produced by Turner et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This is an Open Access publication distributed under the terms of the Creative Commons Attribution CC BY 4.0 licence, which permits unrestricted use, distribution, reproduction and adaption in any medium and for any purpose provided that it is properly attributed. See: https://creativecommons.org/licenses/by/4.0/. For attribution the title, original author(s), the publication source – NIHR Journals Library, and the DOI of the publication must be cited.)
Databáze:	MEDLINE
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