Endotyping of Ventilator-associated Pneumonia With Proteomics on Bronchoalveolar Lavage for Improved Diagnosis, the ClusterVAP Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- Region Skane
- 入组人数
- 400
- 试验地点
- 4
- 主要终点
- Distribution of patients into biologically distinct clusters ("pneumoclusters") based on BAL proteomic data
研究概览
简要总结
Ventilator-associated pneumonia (VAP) is a common and serious infection in patients receiving mechanical ventilation in intensive care units. Current diagnostic methods are imprecise, leading to unnecessary antibiotic use and delayed treatment. The ClusterVAP study aims to identify biologically and clinically distinct subgroups of patients with suspected VAP by analyzing proteins in bronchoalveolar lavage (BAL) fluid using advanced proteomic techniques. This multicentre observational study will enroll approximately 400 adult patients from intensive care units in Sweden, France, Portugal, Denmark, and the United Kingdom. BAL or mini-BAL samples collected for clinical reasons will be analyzed to define "pneumoclusters" and explore their association with patient outcomes. The study will also identify candidate biomarkers that could support future diagnostic tools. No experimental treatments are given; all patients receive standard care. Results may improve diagnostic accuracy and guide personalized treatment strategies for critically ill patients.
详细描述
ClusterVAP is an exploratory, observational, prospective, multicentre cross-sectional study designed to identify biologically and clinically distinct subgroups ("pneumoclusters") among patients with suspected ventilator-associated pneumonia (VAP). The study will enroll approximately 400 adult patients admitted to intensive care units in Sweden, France, Portugal, Denmark, and the United Kingdom who are receiving mechanical ventilation and undergo bronchoalveolar lavage (BAL) or mini-BAL for clinical reasons.
Residual BAL supernatant will be processed for proteomic analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS). Unsupervised consensus clustering will be applied to proteomic data, alone and in combination with clinical and microbiological variables, to define pneumoclusters. These clusters will be characterized by clinical features, microbiology, and radiology, and compared for 30-day outcomes including mortality, ventilator-free days, antibiotic-free days, ICU-free days, and hospital-free days. Differential protein abundance analysis will be used to identify candidate biomarkers for pragmatic cluster assignment.
Data will be collected in electronic case report forms hosted in REDCap, with built-in quality checks. All data will be pseudonymized, and biological samples will be stored under controlled conditions for up to ten years for confirmatory analyses. No experimental interventions are administered; all patients receive standard care. The study has been approved by the Swedish Ethical Review Authority (Dnr 2025-04564-01) and equivalent bodies in participating countries. Results will be disseminated through peer-reviewed publications and scientific conferences, with statistical code shared for transparency.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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 patients (≥18 years) admitted to an intensive care unit (ICU). Receiving invasive mechanical ventilation. Undergoing bronchoalveolar lavage (BAL) or mini-BAL on clinical indication for suspected lower respiratory tract infection.
- •New or worsening clinical signs compatible with lower respiratory tract infection within the preceding 24 hours, defined as the treating clinician's suspicion plus at least one of:
- •Body temperature >38 °C or <36 °C. Visually purulent tracheal secretions. Signs of reduced oxygenation (e.g., increased FiO₂ and/or decreased arterial pO₂, increased positive end-expiratory pressure or driving pressure).
- •Request for chest radiograph to investigate infection or new infiltrate. Initiation of antibiotic therapy targeting lower respiratory tract infection.
排除标准
- •BAL or mini-BAL performed solely for screening without suspicion of infection. Concurrent enrolment in the VAPmarkers study (reserved for external validation).
- •Age <18 years. Any condition that, in the opinion of the investigator, would preclude safe participation or confound study objectives.
结局指标
主要结局
Distribution of patients into biologically distinct clusters ("pneumoclusters") based on BAL proteomic data
时间窗: Day 0 (at enrolment)
Unsupervised consensus clustering of bronchoalveolar lavage (BAL) proteomic profiles, alone and in combination with clinical and microbiological variables, will be performed to classify patients with suspected ventilator-associated pneumonia into biologically distinct clusters ("pneumoclusters"). The number of clusters, the number of patients per cluster, and key distinguishing features will be reported.
次要结局
- Hospital-free days(30 days after enrolment)
- 30-day all-cause mortality(30 days after enrolment)
- Ventilator-free days(30 days after enrolment)
- Antibiotic-free days(30 days after enrolment)
- ICU-free days(30 days after enrolment)