Alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B Trial): protocol for a multicentre phase 3 pragmatic clinical and cost-effectiveness randomised trial in the UK.

Autor:	Walsh TS; The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK twalsh@staffmail.ed.ac.uk., Aitken LM; City University of London, London, UK., McKenzie CA; University of Southampton, Southampton, UK., Boyd J; Edinburgh Clinical Trials Unit, The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK., Macdonald A; The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK., Giddings A; The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK., Hope D; NHS Lothian, Edinburgh, UK., Norrie J; Usher Institute, Edinburgh Clinical Trials Unit, University of Edinburgh No. 9, Bioquarter, Edinburgh, UK., Weir C; Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK., Parker RA; Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh, UK., Lone NI; The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK., Emerson L; City University of London, London, UK., Kydonaki K; Edinburgh Napier University, Edinburgh, UK., Creagh-Brown B; Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK.; Intensive Care Unit, Royal Surrey County Hospital, Guildford, UK., Morris S; Primary Care Unit, University of Cambridge, Cambridge, UK., McAuley DF; Centre for Experimental Medicine, Queen's University Belfast, Belfast, UK., Dark P; Intensive Care Unit, University of Manchester, Greater Manchester, UK., Wise MP; Department of Adult Critical Care, University Hospital of Wales, Cardiff, UK., Gordon AC; Section of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK., Perkins G; Clinical Trials Unit, University of Warwick, Birmingham, UK., Reade M; University of Queensland, Brisbane, Queensland, Australia., Blackwood B; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK., MacLullich A; Geriatric Medicine Unit, University of Edinburgh, Edinburgh, UK., Glen R; NHS Lothian, Edinburgh, UK., Page VJ; Intensive Care, West Hertfordshire Hospitals NHS Trust, Watford, UK.; Faculty of Medicine, Imperial College London, London, UK.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2023 Dec 10; Vol. 13 (12), pp. e078645. Date of Electronic Publication: 2023 Dec 10.
DOI:	10.1136/bmjopen-2023-078645
Abstrakt:	Introduction: Almost all patients receiving mechanical ventilation (MV) in intensive care units (ICUs) require analgesia and sedation. The most widely used sedative drug is propofol, but there is uncertainty whether alpha2-agonists are superior. The alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B) trial aims to determine whether clonidine or dexmedetomidine (or both) are clinically and cost-effective in MV ICU patients compared with usual care. Methods and Analysis: Adult ICU patients within 48 hours of starting MV, expected to require at least 24 hours further MV, are randomised in an open-label three arm trial to receive propofol (usual care) or clonidine or dexmedetomidine as primary sedative, plus analgesia according to local practice. Exclusions include patients with primary brain injury; postcardiac arrest; other neurological conditions; or bradycardia. Unless clinically contraindicated, sedation is titrated using weight-based dosing guidance to achieve a Richmond-Agitation-Sedation score of -2 or greater as early as considered safe by clinicians. The primary outcome is time to successful extubation. Secondary ICU outcomes include delirium and coma incidence/duration, sedation quality, predefined adverse events, mortality and ICU length of stay. Post-ICU outcomes include mortality, anxiety and depression, post-traumatic stress, cognitive function and health-related quality of life at 6-month follow-up. A process evaluation and health economic evaluation are embedded in the trial.The analytic framework uses a hierarchical approach to maximise efficiency and control type I error. Stage 1 tests whether each alpha2-agonist is superior to propofol. If either/both interventions are superior, stages 2 and 3 testing explores which alpha2-agonist is more effective. To detect a mean difference of 2 days in MV duration, we aim to recruit 1437 patients (479 per group) in 40-50 UK ICUs. Ethics and Dissemination: The Scotland A REC approved the trial (18/SS/0085). We use a surrogate decision-maker or deferred consent model consistent with UK law. Dissemination will be via publications, presentations and updated guidelines. Trial Registration Number: ClinicalTrials.gov NCT03653832. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)
Databáze:	MEDLINE
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