基于生物标志物排除呼吸机相关性肺炎以减少抗生素使用的有效性（VAPrapid-2）：一项随机对照试验的研究方案
Effectiveness of biomarker-based exclusion of ventilator-acquired pneumonia to reduce antibiotic use (VAPrapid-2): study protocol for a randomised controlled trial.
作者信息
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
机构信息
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Centre for Population Health Sciences, University of Edinburgh, Medical School, Edinburgh, UK.
出版信息
Trials. 2016 Jul 16;17(1):318. doi: 10.1186/s13063-016-1442-x.
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.
背景
呼吸机相关性肺炎（VAP）是重症监护病房（ICU）进行抗菌治疗的常见原因。基于生物标志物的诊断方法可通过快速排除VAP来改善抗菌药物管理。支气管肺泡灌洗（BAL）液生物标志物此前已被证明能够高度可靠地排除VAP。
方法/设计：这是一项前瞻性、多中心、随机对照试验，旨在确定基于生物标志物的VAP快速排除方法是否能减少抗生素使用并改善抗菌药物管理。临床疑似VAP的患者接受BAL检查，若每毫升痰液中潜在病原体的菌落形成单位（CFU/ml）≥10⁴，则确诊为VAP。患者按1:1随机分组，一组接受“基于生物标志物的抗生素使用建议”，除常规微生物检测外，还对BAL液进行白细胞介素-1β（IL-1β）和白细胞介素-8（IL-8）检测；另一组接受“常规抗生素使用”，即BAL仅进行常规微生物检测。临床团队在随机分组后6小时内对干预措施不知情，之后向临床医生报告生物标志物检测结果。主要结局指标是BAL后7天内无抗生素使用天数（AFD）频率分布的变化。次要结局指标包括14天和28天时的抗生素使用情况；无呼吸机天数；28天死亡率和ICU死亡率；第3天、第7天和第14天的序贯器官衰竭评估（SOFA）；重症监护和住院时间；抗生素相关感染；直至出院、死亡或56天时的耐抗生素病原体培养情况。将根据重症监护和住院时间进行医疗资源利用分析。此外，将收集有关进行BAL的安全性数据。需要210例样本量来检测AFD分布的临床显著变化，即更多患者使用更少抗生素，从而有更多AFD。
讨论
本试验将检验基于生物标志物的VAP快速排除方法是否能使抗生素快速停用，进而改善疑似VAP患者的抗生素管理。
试验注册
ISRCTN65937227。于2013年8月22日注册。ClinicalTrials.gov，NCT01972425。于2013年10月24日注册。
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