ClusterVAP: Multicentre Proteomic Endotyping of Ventilator-associated Pneumonia

Официальное название

Endotyping of Ventilator-associated Pneumonia With Proteomics on Bronchoalveolar Lavage for Improved Diagnosis, the ClusterVAP Study

Обзор

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.

Подробное описание

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.

Первичные конечные точки

• Distribution of patients into biologically distinct clusters ("pneumoclusters") based on BAL proteomic data [Срок оценки: Day 0 (at enrolment)]

Вторичные конечные точки (5)

• 30-day all-cause mortality [Срок оценки: 30 days after enrolment]
• Ventilator-free days [Срок оценки: 30 days after enrolment]
• Antibiotic-free days [Срок оценки: 30 days after enrolment]
• ICU-free days [Срок оценки: 30 days after enrolment]
• Hospital-free days [Срок оценки: 30 days after enrolment]

Критерии участия

Критерии включения

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.

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Швеция · 2 центра

• Skånes universitetssjukhus — Lund
• Karolinska universitetssjukhuset — Stockholm

Франция · 1 центр

• CHU Limoges — Limoges

Португалия · 1 центр

• Hospital de São Francisco Xavier — Lisbon

Публикации

• Sjovall F, Povoa P, Petersson J, Koulenti D, Hernandez Padilla AC, Vaidie J, Lind A, Boetius Hertz F, Paulsson M. ClusterVAP: study protocol for multicentre proteomic endotyping of ventilator-associated pneumonia. BMJ Open Respir Res. 2026 Mar 9;13(1):e003830. doi: 10.1136/bmjresp-2025-003830. PMID 41802817

Идентификаторы

NCT: NCT07245888 · 2025-04564-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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