Pre-clinical Diagnosis Using Integrated Microbial and Host Response Signatures to Improve Outcomes From Ventilator-associated Pneumonia in Critically Ill Children

NCT07026656 | Recruiting

• 1 other identifier: IRAS number: 333103
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Ventilator-associated pneumonia (VAP), defined as pneumonia occurring 48 hours after initiation of invasive mechanical ventilation, is insidious in onset and severe in consequence. It is a critical issue affecting 10-20% of the 26,000 children admitted to the paediatric intensive care unit (PICU) each year. Infection typically leads to extended PICU stay, prolonged invasive mechanical ventilation, and increased mortality. Despite its clinical significance, VAP remains poorly defined, as current diagnosis relies on non-specific criteria and the ability to obtain clinically meaningful cultures. VAP, deviates from conventional pneumonia, potentially originating, from tissue damage, changes to immune processes, and migration of gastrointestinal bacteria into the lung; all associated with prolonged mechanical ventilation. These factors, in combination with the clinical instability of PICU patients, mean that clinicians aggressively start antibiotic therapy despite a paucity of evidence to suggest the best regime. As a result, suspected VAP has been shown to account for nearly 40% of antibiotic exposure in the PICU, which has significant implications on anti-microbial resistance (AMR). To address these challenges, novel diagnostic therapies are needed to optimise the treatment of VAP. These therapies should utilise our current understanding of the pathophysiology of VAP development, specifically, the infiltration of the lung microbiome by gut and oral bacteria during prolonged mechanical ventilation. To achieve this, molecular testing should be promoted allowing for rapid identification of lung pathogens. There is also growing evidence, for the investigation of predictive biomarkers for VAP available in both the blood and lungs, which when integrated into protocols may enhance diagnostic accuracy. These novel techniques may improve clinical outcomes for affected children while addressing the economic impact of prolonged hospital stays and mitigating AMR risks in PICUs.

Conditions

Ventilator Associated Pneumonia ( VAP)

Keywords

Respiratory Tract Infection; Immunology; Genomics; Paediatric Intensive Care Unit (PICU)

Outcome Measures

Primary Outcomes (3)

• Characterise temporal shifts in microbial composition and the corresponding host immune response during prolonged mechanical ventilation

  Serial metagenomic profiling of the lung microbiome to establish microbial shifts. Concurrently, cytokines collected from blood and endotracheal aspirates will be taken to assess immune changes.

  3 years

• Characterise the AMR burden in VAP and its role in shaping the microbiome during infection.

  Utilise metagenomic sequencing to identify AMR genes present on microbes and relate this to VAP development

  3 years

• Develop statistical and/or machine learning models leveraging these signatures independently, or in combination, to identify putative microbial and host biomarkers for early VAP diagnosis

  3 years

Secondary Outcomes (6)

• Prevalence of VAP

  3 years

• 30 day mortality

  3 years

• Time To Extubation

  3 years

• Utilisation Of VAP Prevention Bundle

  3 years

• Culture Results

  3 years

Study Arms (2)

Ventilator Associated Pneumonia Group

Critically ill children who develop VAP during their PICU journey will be assigned to the VAP group

Non-Ventilator Associated Pneumonia Group

All patients who fit eligibility criteria for study and do not go on to develop VAP

Eligibility Criteria

• Age: 1 Month - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Critically Ill Children Requiring Mechanical Ventilation For Greater Than 48 Hours

You may qualify if:

• PICU Admission
• Requires 48 Hours Of Mechanical Ventilation

You may not qualify if:

• Imminent death or palliative care pathway planned
• Existing tracheostomy at time of admission
• Known immunocompromised patient
• Patient received a full course of systemic antimicrobials in the previous 6 weeks.
• Known or suspected tuberculosis (TB).

Sponsors & Collaborators

• University of Cambridge: lead
• Cambridge University Hospitals NHS Foundation Trust: collaborator

Study Sites (1)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Endotracheal Aspirate Oropharyngeal Swab Heparinized Blood PAXgene Whole Blood In Cytodelic Stabilizer

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Respiratory Tract Infections

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Nazima Pathan, FRCPCH PhD

  Department of Paediatrics, University of Cambridge

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nazima Pathan, FRCPCH PhD

CONTACT

+441223 805000; np409@medschl.cam.ac.uk

Don Laing, MBChB, BMedSci (Hons)

CONTACT

+441223 805000; dml57@cam.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: FRCPCH PhD

Study Record Dates

• First Submitted: June 10, 2025
• First Posted: June 18, 2025
• Study Start: April 14, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)