Microbiome-guided Prophylaxis to Reduce Ventilator-Associated Pneumonia in Intensive Care Units: A Pilot Randomized Controlled Trial

NCT07463339 | Not Yet Recruiting Phase 2

• 1 other identifier: REB25-1758
• Study Type: interventional
• Target: 70
• Locations: 0 countries
• Sites: N/A

Brief Summary

Ventilator-associated pneumonia (VAP) remains the most common hospital-acquired infection worldwide, affecting up to 40% of mechanically ventilated patients and contributing to increased morbidity, prolonged hospital stays, and high mortality rates. Standard prevention strategies rely on VAP prevention "bundles", which focus on general supportive care measures such as head-of-bed elevation, sedation interruption, and oral care. While these measures reduce some risk, they do not specifically target the underlying microbial mechanisms driving VAP. Emerging evidence supports the use of inhaled antibiotic (iABx) prophylaxis to suppress or eliminate airway pathogens. Several randomized controlled trials have shown that inhaled antimicrobials can reduce the incidence of VAP. However, the effectiveness of this approach is inconsistent when applied to all ventilated patients. Studies indicate that the greatest benefit occurs when inhaled antimicrobials are targeted toward patients with airway colonization by specific VAP pathogens. Traditional airway microbiome diagnostics have been a major barrier to implementing targeted prophylaxis because they are slow, costly, and require advanced expertise. Recently, a novel diagnostic method-ON-Time rapid microbiome sequencing-has been developed, offering accurate, cost-effective, and rapid (approximately 4.2 hours) results that can identify key VAP pathogens within the airway microbiome of ICU patients such as Enterobacteriaceae organisms, Pseudomonas spp., Acinetobacter spp., Stenotrophomonas maltophilia, Staphylococcus aureus, and others. The ability to define the airway microbiome of ICU patients including whether they harbour potential VAP pathogens provides a unique opportunity to tailor prophylactic antibiotics in a personalized and timely manner. Thus, microbiome-guided prophylaxis represents a novel precision medicine approach to preventing VAP by selecting the right patient. This pilot trial aims to test the feasibility of implementing such an approach to prevent VAP in critically ill patients.

Conditions

Critical Illness; Mechanical Ventilation

Keywords

Ventilator-associated pneumonia; Microbiome; Critical Illness; Inhaled Antibiotics

Outcome Measures

Primary Outcomes (2)

• Feasibility: Adherence to protocol as measured by proportion of participants with endotracheal aspirate (ETA) microbiome sequencing results and initiation of microbiome-guided inhaled antimicrobial prophylaxis (or placebo) within <36h from ICU admission.

  Proportion of participants with endotracheal aspirate (ETA) microbiome sequencing results and initiation of microbiome-guided inhaled antimicrobial prophylaxis (or placebo) within \<36h from ICU admission.

  ICU admission to hour 36.

• Safety: As defined by proportion of participants who develop treatment-emergent adverse events (TEAE) related to inhaled antimicrobials (or placebo).

  Proportion of participants who develop treatment-emergent adverse events (TEAE) related to inhaled antimicrobials (or placebo).

  Enrolment to day 7

Secondary Outcomes (11)

• Ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP)

  Enrolment to day 28

• All-cause mortality

  Enrolment to day 28

• VAP/HAP-free survival

  Enrolment to day 28

• Ventilator-free day

  Enrolment to day 28

• ICU-free and hospital-free days

  Enrolment to day 28

Other Outcomes (1)

• Biological (microbiome and immune) outcomes

  Enrolment to day 14

Study Arms (2)

Microbiome-guided inhaled antibiotic prophylaxis

EXPERIMENTAL

Participants randomized to "microbiome-guided antibiotic prophylaxis" will be administered inhaled antibiotics tailored to their airway microbiome composition.

Drug: Microbiome-guided inhaled antibiotic prophylaxis

Placebo control

PLACEBO COMPARATOR

Participants randomized to "placebo control" will be administered inhaled 0.9% saline placebo.

Drug: Placebo

Interventions

Microbiome-guided inhaled antibiotic prophylaxis DRUG

Participants will receive inhaled antibiotics (tobramycin, aztreonam, and/or vancomycin - based on protocolled matching of VAP pathogens to appropriate antibiotics) for up to 5 days guided by analysis of airway microbiome composition.

Microbiome-guided inhaled antibiotic prophylaxis

Placebo DRUG

Participants randomized to "placebo control" arm will receive inhaled placebo twice daily for 5 days.

Placebo control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (\>18 years old) admitted to FMC ICU
• Mechanically ventilated via endotracheal tube
• Expected duration of mechanical ventilation \>72 hours (as determined by the attending ICU physician)

You may not qualify if:

• Goals of care designation that limits the use of life-sustaining interventions
• Life expectancy \<72 hours (in the opinion of the attending ICU physician)
• Suspected or confirmed pneumonia (community-acquired \[CAP\], hospital-acquired \[HAP\], or ventilator-associated \[VAP\])
• Severe chronic lung disease (diagnosis of chronic lung disease with home oxygen or home mechanical ventilation, or FEV1 \<30% on outpatient pulmonary function testing, or medical research council dyspnea scale grade 4 or higher symptoms attributed to lung disease)
• Contraindication to interventional agents: for inhaled tobramycin - severe acute kidney injury (AKI, KDIGO stage 3) or chronic kidney disease (CKD, stage 4 or higher with eGFR \<30 mL/min measured as outpatient) not receiving renal replacement therapy (RRT), severe allergy/hypersensitivity to aminoglycosides; for aztreonam - severe allergy/hypersensitivity to beta-lactams, for vancomycin - severe allergy/hypersensitivity.
• Tracheostomy
• Pregnancy
• \>48 hours from initiation of mechanical ventilation at the time of enrolment
• Concurrently enrolled in another interventional clinical trial of antimicrobial or immune modulator therapy

Sponsors & Collaborators

• University of Calgary: lead

MeSH Terms

Conditions

Critical Illness; Pneumonia, Ventilator-Associated

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Braedon McDonald, MD, PhD, FRCPC

CONTACT

403-220-6885; bamcdona@ucalgary.ca

Ranjani Somayaji, BScPT, MD, MPH, FRCPC

CONTACT

403-220-8559; rsomayaj@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2026
• First Posted: March 11, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2028
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share