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

INHALE WP3 Study Group and Committees

doi:10.1007/s00134-024-07772-2

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

INHALE WP3 Study Group and Committees

University College London
University of East Anglia
University College London Hospitals
Chelsea and Westminster Hospital NHS Foundation Trust
Department of Critical Care, Royal Brompton and Harefield Foundation Trust, London, UK.
Aintree University Hospital
UCL Great Ormond St Institute of Child Health NIHR Biomedical Research Centre
Microbiology and Infectious Diseases, Barts Health NHS Trust, London, UK.
St George's University Hospitals NHS Foundation Trust
Hampshire Hospitals NHS Foundation Trust
Global Operations, UK Health Security Agency, Porton Down, UK.
Portsmouth Hospitals University NHS Trust
University Hospitals of North Midlands NHS Trust
Birmingham Children's Hospital NHS Foundation Trust
Intensive Care Unit, Royal Free London NHS Foundation Trust, London, UK.
Liverpool University Hospitals NHS Foundation Trust
University of Liverpool
West Hertfordshire Teaching Hospitals NHS Trust
BUPA Cromwell Hospital

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	e172352
Pages (from-to)	272-286
Number of pages	15
Journal	Intensive Care Medicine
Volume	51
Issue number	2
Early online date	17 Feb 2025
DOIs	https://doi.org/10.1007/s00134-024-07772-2
Publication status	Published - 17 Feb 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Critical Care and Intensive Care Medicine

Keywords

Adult
Aged
Anti-Bacterial Agents/therapeutic use
Antimicrobial Stewardship/methods
Child
Female
Healthcare-Associated Pneumonia/drug therapy
Humans
Intensive Care Units/statistics & numerical data
Length of Stay/statistics & numerical data
Male
Middle Aged
Pneumonia, Ventilator-Associated/drug therapy
Polymerase Chain Reaction/methods
Standard of Care
Treatment Outcome
Molecular diagnostics
Rapid PCR
Ventilator-associated pneumonia (VAP)
Hospital-acquired pneumonia (HAP)
Syndromic PCR
Antibiotic stewardship
Point-of-care

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INHALE WP3 Study Group and Committees (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(2), 272-286. Article e172352. https://doi.org/10.1007/s00134-024-07772-2

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title = "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",

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.",

keywords = "Adult, Aged, Anti-Bacterial Agents/therapeutic use, Antimicrobial Stewardship/methods, Child, Female, Healthcare-Associated Pneumonia/drug therapy, Humans, Intensive Care Units/statistics \& numerical data, Length of Stay/statistics \& numerical data, Male, Middle Aged, Pneumonia, Ventilator-Associated/drug therapy, Polymerase Chain Reaction/methods, Standard of Care, Treatment Outcome, Molecular diagnostics, Rapid PCR, Ventilator-associated pneumonia (VAP), Hospital-acquired pneumonia (HAP), Syndromic PCR, Antibiotic stewardship, Point-of-care",

author = "\{INHALE WP3 Study Group and Committees\} and Enne, \{Virve I\} and Susan Stirling and Barber, \{Julie A\} and Juliet High and Charlotte Russell and David Brealey and Zaneeta Dhesi and Antony Colles and Suveer Singh and Robert Parker and Mark Peters and Cherian, \{Benny P\} and Peter Riley and Matthew Dryden and Ruan Simpson and Nehal Patel and Jane Cassidy and Daniel Martin and Welters, \{Ingeborg D\} and Valerie Page and Hala Kandil and Eleanor Tudtud and David Turner and Robert Horne and Justin O'Grady and Swart, \{Ann Marie\} and Livermore, \{David M\} and Vanya Gant",

note = "{\textcopyright} 2025. The Author(s).",

year = "2025",

month = feb,

day = "17",

doi = "10.1007/s00134-024-07772-2",

language = "English",

volume = "51",

pages = "272--286",

journal = "Intensive Care Medicine",

issn = "0342-4642",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "2",

}

INHALE WP3 Study Group and Committees 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, vol. 51, no. 2, e172352, pp. 272-286. https://doi.org/10.1007/s00134-024-07772-2

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. / INHALE WP3 Study Group and Committees.
In: Intensive Care Medicine, Vol. 51, No. 2, e172352, 17.02.2025, p. 272-286.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - INHALE WP3 Study Group and Committees

AU - Enne, Virve I

AU - Stirling, Susan

AU - Barber, Julie A

AU - High, Juliet

AU - Russell, Charlotte

AU - Brealey, David

AU - Dhesi, Zaneeta

AU - Colles, Antony

AU - Singh, Suveer

AU - Parker, Robert

AU - Peters, Mark

AU - Cherian, Benny P

AU - Riley, Peter

AU - Dryden, Matthew

AU - Simpson, Ruan

AU - Patel, Nehal

AU - Cassidy, Jane

AU - Martin, Daniel

AU - Welters, Ingeborg D

AU - Page, Valerie

AU - Kandil, Hala

AU - Tudtud, Eleanor

AU - Turner, David

AU - Horne, Robert

AU - O'Grady, Justin

AU - Swart, Ann Marie

AU - Livermore, David M

AU - Gant, Vanya

PY - 2025/2/17

Y1 - 2025/2/17

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Anti-Bacterial Agents/therapeutic use

KW - Antimicrobial Stewardship/methods

KW - Child

KW - Female

KW - Healthcare-Associated Pneumonia/drug therapy

KW - Humans

KW - Intensive Care Units/statistics & numerical data

KW - Length of Stay/statistics & numerical data

KW - Male

KW - Middle Aged

KW - Pneumonia, Ventilator-Associated/drug therapy

KW - Polymerase Chain Reaction/methods

KW - Standard of Care

KW - Treatment Outcome

KW - Molecular diagnostics

KW - Rapid PCR

KW - Ventilator-associated pneumonia (VAP)

KW - Hospital-acquired pneumonia (HAP)

KW - Syndromic PCR

KW - Antibiotic stewardship

KW - Point-of-care

UR - https://pearl.plymouth.ac.uk/pms-research/1811/

U2 - 10.1007/s00134-024-07772-2

DO - 10.1007/s00134-024-07772-2

M3 - Article

C2 - 39961847

SN - 0342-4642

VL - 51

SP - 272

EP - 286

JO - Intensive Care Medicine

JF - Intensive Care Medicine

IS - 2

M1 - e172352

ER -

INHALE WP3 Study Group and Committees. 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. 2025 Feb 17;51(2):272-286. e172352. Epub 2025 Feb 17. doi: 10.1007/s00134-024-07772-2

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

Abstract

UN SDGs

ASJC Scopus subject areas

Keywords

Access to Document

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