Clinical trial NCT07026656: Pre-clinical Diagnosis Using Integrated Microbial and Host Response Signatures to Improve Outcomes From Ventilator-associated Pneumonia in Critically Ill Children
Official title: Pre-clinical Diagnosis Using Integrated Microbial and Host Response Signatures to Improve Outcomes From Ventilator-associated Pneumonia in Critically Ill Children
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ventilator Associated Pneumonia ( VAP)
Keywords: Respiratory Tract Infection
Paediatric Intenstive Care Unit (PICU)
Ventilator Associated Pneumonia
Immunology
Genomics
Lead sponsor: University of Cambridge
Sponsor class: OTHER
Collaborators: name: Cambridge University Hospitals NHS Foundation Trust
First posted: 2025-06-18
Enrollment: 300
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Critically Ill Children Requiring Mechanical Ventilation For Greater Than 48 Hours

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 consequences. 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. Resultingly, 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.


Eligibility criteria: Inclusion Criteria:

* PICU Admission
* Requires 48 Hours Of Mechanical Ventilation

Exclusion Criteria:

* 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).

Primary outcomes:
measure: Characterise temporal shifts in microbial composition and the corresponding host immune response during prolonged mechanical ventilation
timeFrame: 3 years
measure: Characterise the AMR burden in VAP and its role in shaping the microbiome during infection.
timeFrame: 3 years
measure: 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
timeFrame: 3 years
Secondary outcomes:
measure: Prevalence of VAP
timeFrame: 3 years
measure: 30 day mortality
timeFrame: 3 years
measure: Time To Extubation
timeFrame: 3 years
measure: Utilisation Of VAP Prevention Bundle
timeFrame: 3 years
measure: Culture Results
timeFrame: 3 years
measure: Days free of antimicrobial therapy in PICU at 7 days
timeFrame: 3 years
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
Study officials:
affiliation: Department of Paediatrics, University of Cambridge
name: Nazima Pathan, FRCPCH PhD
role: PRINCIPAL_INVESTIGATOR
References: