{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:30:10Z","timestamp":1790440210566,"version":"4.1.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007602","name":"Programme Grants for Applied Research","doi-asserted-by":"publisher","award":["RP-PG-0514-20018"],"award-info":[{"award-number":["RP-PG-0514-20018"]}],"id":[{"id":"10.13039\/501100007602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Hospital-acquired and ventilator-associated pneumonias (HAP and VAP) are common in critical care and can be life-threatening. Rapid microbiological diagnostics, linked to an algorithm to translate their results into antibiotic choices, could simultaneously improve patient outcomes and antimicrobial stewardship.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The INHALE Randomised Controlled Trial is a multi-centre, parallel study exploring the potential of the BioFire FilmArray molecular diagnostic to guide antibiotic treatment of HAP\/VAP in intensive care units (ICU); it identifies pathogens and key antibiotic resistance in around 90\u2009min. The comparator is standard care whereby the patient receives empirical antibiotics until microbiological culture results become available, typically after 48\u201372\u2009h. Adult and paediatric ICU patients are eligible if they are about to receive antibiotics for a suspected lower respiratory infection (including HAP\/VAP) for the first time or a change in antibiotic because of a deteriorating clinical condition. Breathing spontaneously or intubated, they must have been hospitalised for 48\u2009h or more. Patients are randomised 1:1 to receive either antibiotics guided by the FilmArray molecular diagnostic and its trial-based prescribing algorithm or standard care, meaning empirical antibiotics based on local policy, adapted subsequently based upon local microbiology culture results. Co-primary outcomes are (i) non-inferiority in clinical cure of pneumonia at 14\u2009days post-randomisation and (ii) superiority in antimicrobial stewardship at 24\u2009h post-randomisation (defined as % of patients on active and proportionate antibiotics). Secondary outcomes include further stewardship reviews; length of ICU stay; co-morbidity indicators, including septic shock, change in sequential organ failure assessment scores, and secondary pneumonias; ventilator-free days; adverse events over 21\u2009days; all-cause mortality; and total antibiotic usage. Both cost-effectiveness of the molecular diagnostic-guided therapy and behavioural aspects determining antibiotic prescribing are being explored. A sample size of 552 will be required to detect clinically significant results with 90% power and 5% significance for the co-primary outcomes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>This trial will test whether the potential merits of rapid molecular diagnostics for pathogen and resistance detection in HAP\/VAP are realised in patient outcomes and\/or improved antibiotic stewardship.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>ISRCTN Registry <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/doi.org\/10.1186\/ISRCTN16483855\">ISRCTN16483855<\/jats:ext-link>. Retrospectively registered on 15 July 2019<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-021-05618-6","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T18:03:25Z","timestamp":1633629805000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["INHALE: the impact of using FilmArray Pneumonia Panel molecular diagnostics for hospital-acquired and ventilator-associated pneumonia on antimicrobial stewardship and patient outcomes in UK Critical Care\u2014study protocol for a multicentre randomised controlled trial"],"prefix":"10.1186","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2555-2349","authenticated-orcid":false,"given":"Juliet","family":"High","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virve I.","family":"Enne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Barber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brealey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Horne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaneeta","family":"Dhesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam P.","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa M.","family":"Pandolfo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"Stirling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Russell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"O\u2019Grady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann Marie","family":"Swart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanya","family":"Gant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Livermore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"INHALE Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"5618_CR1","doi-asserted-by":"publisher","first-page":"e3325","DOI":"10.1136\/bmj.e3325","volume":"344","author":"JD Hunter","year":"2012","unstructured":"Hunter JD. 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It was developed with reference to the SPIRIT [] and TIDieR guidelines [].An Independent Data Monitoring Committee (DMC) has been convened to monitor the safety and progress of the trial, including adverse events and antibiotic-related side effects as well as significant patterns in the effectiveness of each treatment arm. In conjunction with the Trials Steering Committee (TSC), they can recommend premature closure of the trial following clear evidence of benefit or harm in accordance with their respective Terms of Reference.A key ethical consideration of this trial is that patients in ICUs often lack the capacity to consent for themselves and the trial is to be conducted in an emergency setting, where consent cannot reasonably be taken before intervention. The aims of the trial are incompatible with only entering patients with capacity and who are able to consent quickly, as it is important to ensure that the findings can be generalised to clinical practice. The trial is not looking at an invasive treatment or medicine; the same antibiotics and decisions are available to clinicians at all times, and they may choose to disregard the FilmArray results and algorithm guidance if clinically indicated. Therefore, consent to participate will be obtained as soon as reasonably appropriate and as described within the manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"DML: Advisory Boards or ad hoc consultancy Accelerate, Allecra, Antabio, Centauri, Entasis, GSK, Integra-Holdings, Meiji, Melinta, Menarini, Mutabilis, Nordic, ParaPharm, Pfizer, QPEX, Roche, Russian Direct Investment Fund, Shionogi, Sumitovant, Summit, T.A.Z., Tetraphase, VenatoRx, Wockhardt, Zambon, Paid lectures \u2013 Accelerate, bioMerieux, Beckman Coulter, Cardiome, Cepheid, GSK, Hikma, Merck\/MSD, Menarini, Nordic and Pfizer and Shionogi. Relevant shareholdings or options in Dechra, GSK, Merck, Perkin Elmer, Pfizer and T.A.Z, amounting to <\u200910% of portfolio value. He also has nominated holdings in Avacta, Diaceutics, Evgen, Faron, Genedrive, Renalytics and Synairgen (all with research\/products pertinent to medical and diagnostic innovation) through Enterprise Investment Schemes, but has no authority to trade these shares directly.VE has received speaking honoraria, consultancy fees and in-kind contributions from several diagnostic companies including Curetis GmbH, bioM\u00e9rieux and Oxford Nanopore.DB has received speaking honoraria or consultancy fees from bioM\u00e9rieux, Gilead and T2 Biosystems.JOG has received speaking honoraria, consultancy fees, in-kind contributions or research funding from Oxford Nanopore, Simcere, Becton-Dickinson and Heraeus Medical.VG has received speaking honoraria from BioM\u00e9rieux and support for Conference attendances from Merck\/MSD and Gilead.The other authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"680"}}