Effectiveness of biomarker-based exclusion of ventilator-acquired pneumonia to reduce antibiotic use (VAPrapid-2): study protocol for a randomised controlled trial

Hellyer, Thomas P; Anderson, Niall; Parker, Jennie; Dark, Paul; Broeck, Tina Van Den; Singh, Suveer; McMullan, Ronan; Agus, Ashley; Emerson, Lydia M; Blackwood, Bronagh; Gossain, Savita; Walsh, Tim; Perkins, Gavin D.; Morris, Andrew Conway; McAuley, Daniel F.; Simpson, A. John

doi:10.1186/s13063-016-1442-x

Cited by 18 publications

(14 citation statements)

References 16 publications

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“…A number of individual proteins have been proposed as biomarkers for the presence of VAP, but single biochemical measurements cannot be consistent predictors of either the presence or the severity of VAP [16]. Multibiomarker protein models could be more promising for the risk assessment of the disease [103,144,145]. Lu et al [146] first described the BAL proteome from patients with VAP by identifying 206 proteins and creating a proteome map.…”

Section: Proteomicsmentioning

confidence: 99%

Biomarkers in Pneumonia—Beyond Procalcitonin

Karakioulaki

Stolz

2019

IJMS

101

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Pneumonia is the leading infectious cause of mortality worldwide and one of the most common lower respiratory tract infections that is contributing significantly to the burden of antibiotic consumption. Due to the complexity of its pathophysiology, it is widely accepted that clinical diagnosis and prognosis are inadequate for the accurate assessment of the severity of the disease. The most challenging task for a physician is the risk stratification of patients with community-acquired pneumonia. Herein, early diagnosis is essential in order to reduce hospitalization and mortality. Procalcitonin and C-reactive protein remain the most widely used biomarkers, while interleukin 6 has been of particular interest in the literature. However, none of them appear to be ideal, and the search for novel biomarkers that will most sufficiently predict the severity and treatment response in pneumonia has lately intensified. Although our insight has significantly increased over the last years, a translational approach with the application of genomics, metabolomics, microbiomics, and proteomics is required to better understand the disease. In this review, we discuss this rapidly evolving area and summarize the application of novel biomarkers that appear to be promising for the accurate diagnosis and risk stratification of pneumonia.

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Section: Proteomicsmentioning

confidence: 99%

Biomarkers in Pneumonia—Beyond Procalcitonin

Karakioulaki

Stolz

2019

IJMS

101

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“…The research protocol was approved by the England and Northern Ireland (13/LO/065) and Scotland (13/SS/0074) National Research Ethics Service committees, and the trial protocol has been published previously. 12 Patients or their relatives or representatives gave written informed consent for inclusion in the study.…”

Section: Methodsmentioning

confidence: 99%

“…Models of change in distribution are outlined in the trial protocol. 12 We deemed effect sizes in the region 0·07–0·08 to be of a clinically relevant magnitude. These effect sizes represent an approximate change in median antibiotic-free days from 0 (IQR 0·0–2·5) to 1·5 (0·0–3·5).…”

Section: Methodsmentioning

confidence: 99%

Biomarker-guided antibiotic stewardship in suspected ventilator-associated pneumonia (VAPrapid2): a randomised controlled trial and process evaluation

Hellyer

McAuley

Walsh

et al. 2020

The Lancet Respiratory Medicine

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101

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Background Ventilator-associated pneumonia is the most common intensive care unit (ICU)-acquired infection, yet accurate diagnosis remains difficult, leading to overuse of antibiotics. Low concentrations of IL-1β and IL-8 in bronchoalveolar lavage fluid have been validated as effective markers for exclusion of ventilator-associated pneumonia. The VAPrapid2 trial aimed to determine whether measurement of bronchoalveolar lavage fluid IL-1β and IL-8 could effectively and safely improve antibiotic stewardship in patients with clinically suspected ventilator-associated pneumonia. Methods VAPrapid2 was a multicentre, randomised controlled trial in patients admitted to 24 ICUs from 17 National Health Service hospital trusts across England, Scotland, and Northern Ireland. Patients were screened for eligibility and included if they were 18 years or older, intubated and mechanically ventilated for at least 48 h, and had suspected ventilator-associated pneumonia. Patients were randomly assigned (1:1) to biomarker-guided recommendation on antibiotics (intervention group) or routine use of antibiotics (control group) using a web-based randomisation service hosted by Newcastle Clinical Trials Unit. Patients were randomised using randomly permuted blocks of size four and six and stratified by site, with allocation concealment. Clinicians were masked to patient assignment for an initial period until biomarker results were reported. Bronchoalveolar lavage was done in all patients, with concentrations of IL-1β and IL-8 rapidly determined in bronchoalveolar lavage fluid from patients randomised to the biomarker-based antibiotic recommendation group. If concentrations were below a previously validated cutoff, clinicians were advised that ventilator-associated pneumonia was unlikely and to consider discontinuing antibiotics. Patients in the routine use of antibiotics group received antibiotics according to usual practice at sites. Microbiology was done on bronchoalveolar lavage fluid from all patients and ventilator-associated pneumonia was confirmed by at least 10⁴ colony forming units per mL of bronchoalveolar lavage fluid. The primary outcome was the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage. Data were analysed on an intention-to-treat basis, with an additional per-protocol analysis that excluded patients randomly assigned to the intervention group who defaulted to routine use of antibiotics because of failure to return an adequate biomarker result. An embedded process evaluation assessed factors influencing trial adoption, recruitment, and decision making. This study is registered with ISRCTN, ISRCTN65937227, and ClinicalTrials.gov, NCT01972425. Findings Between Nov 6, 2013, and Sept 13, 2016, 360 patients were screened for inclusion in the study. 146 patients were ineligible, leaving 214 who were recruited to the study. Four patients were excluded before randomisation, meaning that 210 patients were randomly assigned to biomarker-guided recommendation on antibiotics (n=104) or routine us...

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“…Unfortunately, the original version of this article [ 1 ] contained an error. There are two references in the text to the threshold for defining VAP as greater than 10^4 colony forming units/ml.…”

Section: Erratummentioning

confidence: 99%