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

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 > 104 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.

Citation

Hellyer, T. P., Anderson, N. H., Parker, J., Dark, P., Van Den Broeck, T., Singh, S., McMullan, R., Agus, A. M., Emerson, L. M., Blackwood, B., Gossain, S., Walsh, T. S., Perkins, G. D., Conway Morris, A., McAuley, D. F., & Simpson, A. J. (2016). Effectiveness of biomarker-based exclusion of ventilator-acquired pneumonia to reduce antibiotic use (VAPrapid-2): study protocol for a randomised controlled trial. Trials, 17(1), Article 318. https://doi.org/10.1186/s13063-016-1442-x

• Journal Article Type: Article
• Acceptance Date: Jun 24, 2016
• Online Publication Date: Jul 16, 2016
• Publication Date: 2016
• Deposit Date: Jun 2, 2023
• Publicly Available Date: Jun 2, 2023
• Journal: Trials
• Print ISSN: 1745-6215
• Publisher: BMC
• Peer Reviewed: Peer Reviewed
• Volume: 17
• Issue: 1
• Article Number: 318
• DOI: https://doi.org/10.1186/s13063-016-1442-x
• Keywords: Ventilator-acquired pneumonia, Biomarker, Antibiotic stewardship, Randomised controlled trial
• Publisher URL: https://doi.org/10.1186/s13063-016-1442-x