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ToolsEnne, Virve I., Stirling, Susan, Barber, Julie A., High, Juliet, Russell, Charlotte, Brealey, David, Dhesi, Zaneeta, Colles, Antony, Singh, Suveer, Parker, Robert, Peters, Mark, Cherian, Benny P., Riley, Peter, Dryden, Matthew, Simpson, Ruan, Patel, Nehal, Cassidy, Jane, Martin, Daniel, Welters, Ingeborg D., Page, Valerie, Kandil, Hala, Tudtud, Eleanor, Turner, David, Horne, Robert, O'Grady, Justin, Swart, Ann Marie, Livermore, David M. and Gant, Vanya and INHALE WP3 Study 12 Group (2025) INHALE WP3, a multicentre, open-label, pragmatic randomised controlled trial assessing the impact of rapid, ICU-based, syndromic PCR, versus standard-of-care on antibiotic stewardship and clinical outcomes in hospital-acquired and ventilator-associated pneumonia. Intensive Care Medicine, 51. 272–286. ISSN 0342-4642
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Abstract
Purpose: INHALE investigated the impact of seeking pathogens by PCR on antibiotic stewardship and clinical outcomes in hospital-acquired and ventilator-associated pneumonia (HAP and VAP). Methods: This pragmatic multicentre, open-label RCT enrolled adults and children with suspected HAP and VAP at 14 ICUs. Patients were randomly allocated to standard of care, or rapid in-ICU syndromic PCR coupled with optional prescribing guidance. Co-primary outcomes were superiority in antibiotic stewardship at 24 h and non-inferiority in clinical cure of pneumonia 14 days post-randomisation. Secondary outcomes included mortality, ICU length of stay and evolution of clinical scores. Results: 554 eligible patients were recruited from 5th July 2019 to 18th August 2021, with a COVID-enforced pause from 16th March 2020 and 9th July 2020. Data were analysed for 453 adults and 92 children (68.4% male; 31.6% female). ITT analysis showed 205/268 (76.5%) reviewable intervention patients receiving antibacterially appropriate and proportionate antibiotics at 24 h, versus 147/263 (55.9%) standard-of-care patients (estimated difference 21%; 95% CI 13–28%). However, only 152/268 (56.7%) intervention patients were deemed cured of pneumonia at 14 days, versus 171/265 (64.5%) standard-of-care patients (estimated difference − 6%, 95% CI − 15 to 2%; predefined non-inferiority margin -13%). Secondary mortality and ΔSOFA outcomes narrowly favoured the control arm, without clear statistical significance. Conclusions: In-ICU PCR for pathogens resulted in improved antibiotic stewardship. However, non-inferiority was not demonstrated for cure of pneumonia at 14 days. Further research should focus on clinical effectiveness studies to elucidate whether antibiotic stewardship gains achieved by rapid PCR can be safely and advantageously implemented.
| Item Type: | Article |
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| Additional Information: | Data availability statement: The data dictionary and deidentified patient data analysed and presented in this study are available from NCTU following publication, on reasonable request and subject to appropriate data sharing agreements. The statistical analysis plan is publicly available at https://norwichctu.uea.ac.uk/inhale/.” Funding information: This research was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Reference Number: RP-PG-0514-20018). Infrastructure support was provided by the NIHR University College London and Imperial College London Biomedical Research Centres. The views expressed are those of the authors and not necessarily those of the NIHR, or the Department of Health and Social Care. The study funder had no role in design, data collection, data analysis, data interpretation, or writing of the manuscript. biomérieux provided FilmArray Torch instruments, Pneumonia Panel tests and quality control materials free of charge. The manufacturer had no input into the conception, design, data analysis or interpretation of the study and no input into writing of the manuscript. |
| Uncontrolled Keywords: | antibiotic stewardship,hospital-acquired pneumonia (hap),molecular diagnostics,point-of-care,rapid pcr,syndromic pcr,ventilator-associated pneumonia (vap),critical care and intensive care medicine ,/dk/atira/pure/subjectarea/asjc/2700/2706 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit Faculty of Medicine and Health Sciences > Research Groups > Epidemiology and Public Health Faculty of Medicine and Health Sciences > Research Centres > Population Health Faculty of Medicine and Health Sciences > Research Groups > Health Services and Primary Care Faculty of Medicine and Health Sciences > Research Groups > Health Economics Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health |
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| Depositing User: | LivePure Connector |
| Date Deposited: | 07 Jan 2025 02:17 |
| Last Modified: | 28 Mar 2025 13:08 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/98106 |
| DOI: | 10.1007/s00134-024-07772-2 |
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