ClusterVAP: Multicentre Proteomic Endotyping of Ventilator-associated Pneumonia

Region Skane

Status: Not yet enrolling

Conditions: Mechanical Ventilation Complication; Ventilator Acquired Pneumonia

Study type: Observational

Funder types: Other

Identifiers

NCT07245888

2025-04564-01

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

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.

Trial design

400 participants in 1 patient group

Patients with suspected ventilator-associated pneumonia

Description:

Adult ICU patients receiving mechanical ventilation who undergo bronchoalveolar lavage (BAL) or mini-BAL for clinical suspicion of lower respiratory tract infection. Residual BAL fluid will be analyzed using proteomic profiling to identify biological subgroups ("pneumoclusters"). No experimental intervention is administered; all patients receive standard care.