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

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.

• Authors: 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
• Journal: Trials (Trials) Vol. 17 Issue 1 Pg. 318 (07 16 2016) ISSN: 1745-6215 [Electronic] England
• PMID: 27422026 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Anti-Bacterial Agents
• Biomarkers
• CXCL8 protein, human
• IL1B protein, human
• Interleukin-1beta
• Interleukin-8

Topics

• Anti-Bacterial Agents (therapeutic use)
• Antimicrobial Stewardship
• Bacteria (growth & development, isolation & purification)
• Biomarkers (analysis)
• Bronchoalveolar Lavage Fluid (chemistry, microbiology)
• Clinical Protocols
• Colony Count, Microbial
• Hospital Mortality
• Humans
• Interleukin-1beta (analysis)
• Interleukin-8 (analysis)
• Length of Stay
• Organ Dysfunction Scores
• Patient Selection
• Pneumonia, Bacterial (diagnosis, drug therapy, microbiology, mortality)
• Pneumonia, Ventilator-Associated (diagnosis, drug therapy, microbiology, mortality)
• Predictive Value of Tests
• Prospective Studies
• Research Design
• Respiration, Artificial
• Time Factors
• United Kingdom
• Unnecessary Procedures