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
File(s)
Published version
Author(s)
Type
Journal Article
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.
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.
Date Issued
2025-02-01
Date Acceptance
2024-12-22
Citation
Intensive Care Medicine, 2025, 51 (2), pp.272-286
ISSN
0342-4642
Publisher
Springer
Start Page
272
End Page
286
Journal / Book Title
Intensive Care Medicine
Volume
51
Issue
2
Copyright Statement
© 2025 The Author(s) Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39961847
PII: 10.1007/s00134-024-07772-2
Subjects
Antibiotic stewardship
ANTIMICROBIAL STEWARDSHIP
Critical Care Medicine
General & Internal Medicine
Hospital-acquired pneumonia (HAP)
Life Sciences & Biomedicine
Molecular diagnostics
Point-of-care
Rapid PCR
Science & Technology
Syndromic PCR
Ventilator-associated pneumonia (VAP)
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2025-02-17