Microbiome-guided Prophylaxis to Reduce Ventilator-Associated Pneumonia in Intensive Care Units: A Pilot Randomized Controlled Trial (MICRO-VAP)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 70
- 主要终点
- Feasibility: Adherence to protocol as measured by proportion of participants with endotracheal aspirate (ETA) microbiome sequencing results and initiation of microbiome-guided inhaled antimicrobial prophylaxis (or placebo) within <36h from ICU admission.
研究概览
简要总结
Ventilator-associated pneumonia (VAP) remains the most common hospital-acquired infection worldwide, affecting up to 40% of mechanically ventilated patients and contributing to increased morbidity, prolonged hospital stays, and high mortality rates. Standard prevention strategies rely on VAP prevention "bundles", which focus on general supportive care measures such as head-of-bed elevation, sedation interruption, and oral care. While these measures reduce some risk, they do not specifically target the underlying microbial mechanisms driving VAP.
Emerging evidence supports the use of inhaled antibiotic (iABx) prophylaxis to suppress or eliminate airway pathogens. Several randomized controlled trials have shown that inhaled antimicrobials can reduce the incidence of VAP. However, the effectiveness of this approach is inconsistent when applied to all ventilated patients. Studies indicate that the greatest benefit occurs when inhaled antimicrobials are targeted toward patients with airway colonization by specific VAP pathogens.
Traditional airway microbiome diagnostics have been a major barrier to implementing targeted prophylaxis because they are slow, costly, and require advanced expertise. Recently, a novel diagnostic method-ON-Time rapid microbiome sequencing-has been developed, offering accurate, cost-effective, and rapid (approximately 4.2 hours) results that can identify key VAP pathogens within the airway microbiome of ICU patients such as Enterobacteriaceae organisms, Pseudomonas spp., Acinetobacter spp., Stenotrophomonas maltophilia, Staphylococcus aureus, and others. The ability to define the airway microbiome of ICU patients including whether they harbour potential VAP pathogens provides a unique opportunity to tailor prophylactic antibiotics in a personalized and timely manner.
Thus, microbiome-guided prophylaxis represents a novel precision medicine approach to preventing VAP by selecting the right patient. This pilot trial aims to test the feasibility of implementing such an approach to prevent VAP in critically ill patients.
详细描述
Research Question:
Is it feasible and safe to implement a randomized controlled trial of microbiome-guided inhaled antimicrobial prophylaxis to prevent VAP in mechanically ventilated ICU patients?
Primary Objective:
To assess the feasibility of conducting a full-scale randomized controlled trial, including protocol adherence, timely microbiome result reporting, and timely initiation and completion of the assigned intervention, and safety.
Secondary Objectives:
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, Outcomes Assessor)
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
- •Adult (>18 years old) admitted to FMC ICU
- •Mechanically ventilated via endotracheal tube
- •Expected duration of mechanical ventilation >72 hours (as determined by the attending ICU physician)
排除标准
- •Goals of care designation that limits the use of life-sustaining interventions
- •Life expectancy <72 hours (in the opinion of the attending ICU physician)
- •Suspected or confirmed pneumonia (community-acquired [CAP], hospital-acquired [HAP], or ventilator-associated [VAP])
- •Severe chronic lung disease (diagnosis of chronic lung disease with home oxygen or home mechanical ventilation, or FEV1 <30% on outpatient pulmonary function testing, or medical research council dyspnea scale grade 4 or higher symptoms attributed to lung disease)
- •Contraindication to interventional agents: for inhaled tobramycin - severe acute kidney injury (AKI, KDIGO stage 3) or chronic kidney disease (CKD, stage 4 or higher with eGFR <30 mL/min measured as outpatient) not receiving renal replacement therapy (RRT), severe allergy/hypersensitivity to aminoglycosides; for aztreonam - severe allergy/hypersensitivity to beta-lactams, for vancomycin - severe allergy/hypersensitivity.
- •Tracheostomy
- •Pregnancy
- •>48 hours from initiation of mechanical ventilation at the time of enrolment
- •Concurrently enrolled in another interventional clinical trial of antimicrobial or immune modulator therapy
研究组 & 干预措施
Microbiome-guided inhaled antibiotic prophylaxis
Participants randomized to "microbiome-guided antibiotic prophylaxis" will be administered inhaled antibiotics tailored to their airway microbiome composition.
干预措施: Microbiome-guided inhaled antibiotic prophylaxis (Drug)
Placebo control
Participants randomized to "placebo control" will be administered inhaled 0.9% saline placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Feasibility: Adherence to protocol as measured by proportion of participants with endotracheal aspirate (ETA) microbiome sequencing results and initiation of microbiome-guided inhaled antimicrobial prophylaxis (or placebo) within <36h from ICU admission.
时间窗: ICU admission to hour 36.
Proportion of participants with endotracheal aspirate (ETA) microbiome sequencing results and initiation of microbiome-guided inhaled antimicrobial prophylaxis (or placebo) within \<36h from ICU admission.
Safety: As defined by proportion of participants who develop treatment-emergent adverse events (TEAE) related to inhaled antimicrobials (or placebo).
时间窗: Enrolment to day 7
Proportion of participants who develop treatment-emergent adverse events (TEAE) related to inhaled antimicrobials (or placebo).
次要结局
- ICU-free and hospital-free days(Enrolment to day 28)
- Extubation failure(Enrolment to day 28)
- Ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP)(Enrolment to day 28)
- All-cause mortality(Enrolment to day 28)
- VAP/HAP-free survival(Enrolment to day 28)
- Ventilator-free day(Enrolment to day 28)
- Ventilator-associated complications and infection-related ventilator-associated complications(Enrolment to day 28)
- Non-pneumonia hospital-acquired infections (HAIs)(Enrolment to day 28)
- Illness severity(Enrolment to day 28)
- Lung injury severity(Enrolment to day 28)
- Additional safety outcomes(Enrolment to day 28)