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

NCT ID: NCT07026656

Last Updated: 2025-08-03

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-04-14
• Study Completion Date: 2027-09-30

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)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Ventilator Associated Pneumonia Group

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

No interventions assigned to this group

Non-Ventilator Associated Pneumonia Group

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

No interventions assigned to this group

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).

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role: collaborator

University of Cambridge

OTHER

Sponsor Role: lead

Responsible Party

Nazima Pathan

FRCPCH PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nazima Pathan, FRCPCH PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Paediatrics, University of Cambridge

Locations

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Nazima Pathan, FRCPCH PhD

Role: CONTACT

np409@medschl.cam.ac.uk

+441223 805000

Don Laing, MBChB, BMedSci (Hons)

Role: CONTACT

dml57@cam.ac.uk

+441223 805000

Facility Contacts

Nazima Pathan, FRCPCH PhD

Role: primary

np409@medschl.cam.ac.uk

+441223 805000

Other Identifiers

IRAS number: 333103

Identifier Type: -

Identifier Source: org_study_id