A Randomised Controlled Trial of Biomarker-based Exclusion of VAP to Improve Antibiotic Stewardship
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 211
- 试验地点
- 30
- 主要终点
- Antibiotic free days (AFD)
研究概览
简要总结
Critically ill patients whose lungs are supported by breathing machines (ventilators) commonly develop a new lung infection, called ventilator-associated pneumonia (VAP). Because VAP is often fatal, antibiotics are administered whenever it is suspected. However VAP is hard to distinguish from several non-infective lung conditions and most patients with suspected VAP do not have pneumonia. Therefore many patients receive unnecessary antibiotics for several days, promoting emergence of 'superbugs'. Laboratory test results for diagnosing VAP typically only reach the doctors after 3 days.
A simple test rapidly and confidently excluding VAP should improve patient care, reduce unnecessary antibiotics and decrease costs. We recently showed that low levels of specific proteins in fluid from the lungs of patients with suspected VAP effectively excluded VAP, using a test that may yield results within 6 hours. The test used is an extension of existing technology produced by our commercial partner Becton Dickinson (BD) Biosciences.
Our previous findings were derived from a single hospital's intensive care unit. We have recently confirmed this finding across many intensive care units, which will help show that the test can be used in 'real life'. The aim of this study is to take the new test to the next step and determine whether it can improve the care of patients by reducing the amount of unnecessary antibiotics prescribed. This will be done using a 'randomised controlled trial', the best tool for scientifically testing a new diagnostic test. To do this we shall identify patients with suspected VAP, all of whom will have a lung sample - half of the patients will receive 'usual care' for suspected VAP, the other half will have the new test performed on their lung fluid. If the new test suggests no lung infection, the doctors will be asked to consider not giving antibiotics. We shall test how much antibiotic is given to each group.
详细描述
VAP is associated with higher mortality than any other nosocomial infection. Several non-infective conditions mimic VAP and significant infection is usually confirmed in less than 40% of suspected cases. No tests reliably exclude VAP at the point of clinical suspicion, and microbiological results typically return 3 days later. Consequently, while empirical broad-spectrum antibiotics are routinely administered, most patients with suspected VAP do not have pneumonia.
Using cytometric bead array (CBA) technology, we have demonstrated that IL-1b in bronchoalveolar lavage fluid (BALF) can be used to exclude VAP in both a single centre derivation study and a multi-centre validation study. A combination of IL-1b and IL-8 can exclude VAP with a sensitivity of 100%, a specificity of 44.3% and a negative predictive value of 1.
This randomised controlled trial will determine whether a biomarker-based recommendation on antibiotics (versus routine use of antibiotics) will improve antibiotic stewardship in suspected VAP.
This study tests the hypothesis that a 'biomarker-guided recommendation on antibiotics' will improve antibiotic stewardship in patients with suspected VAP while maintaining equivalent patient outcomes.
Recruitment for RCT will end when BAL has been performed on 210 patients. For regulatory purposes, the study will continue until follow up data is collected for the 210th patient.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •are based on those for adults fulfilling criteria for suspected VAP:
- •Age ≥18 years
- •Mechanically ventilated for ≥ 48hrs
- •2 or more of:
- •Temperature <35ºC or >38ºC
- •White cell count <4x109/L or >11x109/L
- •Purulent tracheal secretions
- •New or worsening CXR or CT scan changes
- •The patient is considered suitable for early discontinuation of antibiotics
排除标准
- •are based on features considered to predict poor tolerance of BAL and adapted from our previous studies:
- •PaO2<8kPa on FiO2>0.7
- •Positive end-expiratory pressure >15cmH2O
- •Peak airway pressure >35 cmH2O
- •Heart rate >140 bpm
- •Mean arterial pressure <65mmHg
- •Bleeding diathesis (including platelet count <20x109 per litre of blood or international normalised ratio (INR) >3)
- •Poorly controlled intracranial pressure (>20mmHg)
- •ICU consultant deems procedure not to be safe
- •Previous BAL as part of this study
- •Consent declined
- •Patients who are enrolled in observational studies will be eligible for co-enrolment. Co-enrolment with interventional studies will be possible following consideration of any scientific or statistical interaction, in accordance with current UK critical care research forum (UKCCRF) recommendations (see appendix). Until co-enrolment is considered appropriate for a particular study, patients enrolled in an interventional trial will not be included.
结局指标
主要结局
Antibiotic free days (AFD)
时间窗: 7 days
The frequency distribution of antibiotic-free days (AFD) in the 7 days following BAL
次要结局
未报告次要终点