TY - JOUR
T1 - Effectiveness of a biomarker-based exclusion of ventilator-acquired pneumonia to reduce antibiotic use: protocol for a randomised controlled trial (VAPrapid-2)
T2 - Study protocol for a randomised controlled trial
AU - Hellyer, Thomas P.
AU - Anderson, Niall H.
AU - Parker, Jennie
AU - Dark, Paul
AU - van den Broeck, Tina
AU - Singh, Suveer
AU - McMullan, Ronan
AU - Agus, Ashley
AU - Emerson, Lydia M.
AU - Blackwood, Bronagh
AU - Gossain, Savita
AU - Walsh, Tim
AU - Perkins, Gavin
AU - Conway Morris, Andre
AU - McAuley, Daniel F.
AU - Simpson, A. John
PY - 2016/7/16
Y1 - 2016/7/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84978288383&partnerID=8YFLogxK
U2 - 10.1186/s13063-016-1442-x
DO - 10.1186/s13063-016-1442-x
M3 - Article
AN - SCOPUS:84978288383
VL - 17
JO - Trials
JF - Trials
SN - 1745-6215
IS - 1
M1 - 318
ER -