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

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

Abstract

Background: Ventilator-acquired pneumonia (VAP) is a common reason for antimicrobial therapy in the intensive care unit (ICU). Biomarker-based diagnostics could improve antimicrobial stewardship through rapid exclusion of VAP. Bronchoalveloar lavage (BAL) fluid biomarkers have previously been shown to allow the exclusion of VAP with high confidence.

Methods/design: This is a prospective, multi-centre, randomised, controlled trial to determine whether a rapid biomarker-based exclusion of VAP results in fewer antibiotics and improved antimicrobial management. Patients with clinically suspected VAP undergo BAL, and VAP is confirmed by growth of a potential pathogen at [≥] 10(4) colony-forming units per millilitre (CFU/ml). Patients are randomised 1:1, to either a 'biomarker-guided recommendation on antibiotics' in which BAL fluid is tested for IL-1β and IL-8 in addition to routine microbiology testing, or to 'routine use of antibiotics' in which BAL undergoes routine microbiology testing only. Clinical teams are blinded to intervention until 6 hours after randomisation, when biomarker results are reported to the clinician. The primary outcome is a change in the frequency distribution of antibiotic-free days (AFD) in the 7 days following BAL. Secondary outcome measures include antibiotic use at 14 and 28 days; ventilator-free days; 28-day mortality and ICU mortality; sequential organ failure assessment (SOFA) at days 3, 7 and 14; duration of stay in critical care and the hospital; antibiotic-associated infections; and antibiotic-resistant pathogen cultures up to hospital discharge, death or 56 days. A healthcare-resource-utilisation analysis will be calculated from the duration of critical care and hospital stay. In addition, safety data will be collected with respect to performing BAL. A sample size of 210 will be required to detect a clinically significant shift in the distribution of AFD towards more patients having fewer antibiotics and therefore more AFD.

Discussion: This trial will test whether a rapid biomarker-based exclusion of VAP results in rapid discontinuation of antibiotics and therefore improves antibiotic management in patients with suspected VAP.

Trial registration: ISRCTN65937227 . Registered on 22 August 2013. ClinicalTrials.gov, NCT01972425 . Registered on 24 October 2013.

Keywords: Antibiotic stewardship; Biomarker; Randomised controlled trial; Ventilator-acquired pneumonia.

Figures

Fig. 1
Fig. 1
Consolidated Standards of Reporting Trials (CONSORT) 2010 flow diagram
Fig. 2
Fig. 2
Graphical representation of the shift in distribution in antibiotic-free days (AFD) between baseline and model 3

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Source: PubMed

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