Critical IllnessPhase 2MICRO-VAPNCT07463339
Microbiome-guided Prophylaxis to Reduce Ventilator-Associated Pneumonia in Intensive Care Units: A Pilot Randomized Controlled Trial
A Phase 2 study testing Microbiome-guided inhaled antibiotic prophylaxis in people with Critical Illness and Mechanical Ventilation, run by University of Calgary.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness, Mechanical Ventilation
- What is being tested?
- Microbiome-guided inhaled antibiotic prophylaxis
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- No sites listed yet
- Study dates
- 1 May 2026to 30 Apr 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Microbiome-guided Prophylaxis to Reduce Ventilator-Associated Pneumonia in Intensive Care Units: A Pilot Randomized Controlled Trial (MICRO-VAP)
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.
Read more
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.
Read the detailed description
Research Question:
Is it feasible and safe to implement a randomized controlled trial of microbiome-guided inhaled antimicrobial prophylaxis to prevent VAP in mechanically ventilated ICU patients?
Primary Objective:
To assess the feasibility of conducting a full-scale randomized controlled trial, including protocol adherence, timely microbiome result reporting, and timely initiation and completion of the assigned intervention, and safety.
Secondary Objectives:
To explore the impact of microbiome-guided inhaled prophylaxis on airway microbiome composition and to estimate clinical outcomes including VAP incidence, ventilator-free days, ICU and hospital length of stay, and mortality up to 28 days.
Hypothesis:
Microbiome-guided inhaled antimicrobial prophylaxis is feasible and may be superior to standard care in reducing airway pathogen burden and VAP incidence.
Methods:
This is a single-centre, randomized, placebo-controlled pilot trial enrolling 70 mechanically ventilated adult ICU patients at Foothills Medical Centre in Calgary, AB, Canada. Participants will be randomized 1:1 to microbiome-guided inhaled antibiotic prophylaxis (intervention arm) or matching placebo (control arm). Endotracheal aspirates (ETA) will be collected at enrolment for rapid microbiome sequencing and analysis. In the intervention arm, participants with airway microbiome positive for VAP pathogens will receive inhaled tobramycin, participants with airway S. aureus will receive inhaled vancomycin, while those without pathogens will receive inhaled saline placebo. Treatment responsiveness will be determined on day 3 with repeat airway microbiome sequencing and analysis, and in participants with persistent airway pathogens, inhaled tobramycin will be changed to inhaled aztreonam, while those with airway S. aureus will continue to receive inhaled vancomycin. Total duration of intervention will be 5 days. Participants randomized to control arm, will undergo identical ETA sampling for airway microbiome sequencing but results will remain blinded, and participants will receive inhaled saline placebo for 5 days. Clinicians and participants will be blinded to microbiome results and allocation. Participants will be followed for up to 28 days for primary feasibility and safety outcomes (see section below for additional details), as well as secondary clinical outcomes and biological outcomes (airway microbiome and immune analyses).
- Conditions
- Critical Illness, Mechanical Ventilation
- Being tested
- Microbiome-guided inhaled antibiotic prophylaxis, Placebo
- Keywords
- Ventilator-associated pneumonia, Microbiome, Critical Illness, Inhaled Antibiotics
- Medical subject headings
- Critical Illness, Pneumonia, Ventilator-Associated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Microbiome-guided inhaled antibiotic prophylaxisDrug
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.
PlaceboDrug
Participants randomized to "placebo control" arm will receive inhaled placebo twice daily for 5 days.
| Study group | Role | What they receive |
|---|---|---|
| Microbiome-guided inhaled antibiotic prophylaxis | Experimental | Participants randomized to "microbiome-guided antibiotic prophylaxis" will be administered inhaled antibiotics tailored to their airway microbiome composition. Receives: Drug: Microbiome-guided inhaled antibiotic prophylaxis |
| Placebo control | Placebo comparator | Participants randomized to "placebo control" will be administered inhaled 0.9% saline placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: Enrolment to day 7
Secondary outcomes (11)
Ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP)
Incidence of VAP/HAP from the time of enrolment to day 28, including early-onset VAP/HAP (enrolment to day 4) and late onset VAP/HAP (day 5 to day 28).
Measured: Enrolment to day 28
All-cause mortality
All-cause mortality from enrolment to day 28.
Measured: Enrolment to day 28
VAP/HAP-free survival
Composite outcome of VAP/HAP or death from enrolment to day 28
Measured: Enrolment to day 28
Ventilator-free day
Days free of mechanical ventilation from the time of enrolment to day 28.
Measured: Enrolment to day 28
ICU-free and hospital-free days
Number of days spent outside of ICU and number of days spent outside of hospital from enrolment to day 28
Measured: Enrolment to day 28
Extubation failure
Re-intubation within 7 days following extubation from enrolment to day 28
Measured: Enrolment to day 28
Ventilator-associated complications and infection-related ventilator-associated complications
Incidence of ventilator-associated complications (VAC), and infection-related ventilator-associated complications (IVAC) from enrolment to day 28.
Measured: Enrolment to day 28
Non-pneumonia hospital-acquired infections (HAIs)
Incidence of other hospital-acquired infections (HAIs) from enrolment to day 28
Measured: Enrolment to day 28
Illness severity
Daily maximum sequential organ failure assessment (SOFA) score from enrolment to day 28.
Measured: Enrolment to day 28
Lung injury severity
Daily maximum PaO2/FiO2 and/or SaO2/FiO2 respiratory ratio from the time of enrolment to day 28.
Measured: Enrolment to day 28
Additional safety outcomes
Additional safety outcomes including any serious adverse events (SAEs), degree of hypoxemia (daily PaO2/FiO2 and/or SaO2/FiO2 respiratory ratio), clinically significant bronchospasm, ICU-acquired infections with antibiotic resistant bacteria.
Measured: Enrolment to day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2026
- Study start1 May 2026 (estimated)
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07463339
- Sponsor's protocol ID
- REB25-1758
- Acronym
- MICRO-VAP
- Status last verified
- Mar 2026
- First submitted
- 5 Mar 2026
- Last updated
- 11 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microbiome-guided Prophylaxis to Reduce Ventilator-Associated Pneumonia in Intensive Care Units: A Pilot Randomized Controlled Trial (MICRO-VAP)
- ClinicalTrials.gov ID
- NCT07463339
- Acronym / sponsor ID
- MICRO-VAP / REB25-1758
- Conditions
- Critical Illness, Mechanical Ventilation
- Keywords
- Ventilator-associated pneumonia, Microbiome, Critical Illness, Inhaled Antibiotics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- 1 May 2026 (estimated)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 30 Apr 2028 (estimated)
- First posted
- 11 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Research Question:
Is it feasible and safe to implement a randomized controlled trial of microbiome-guided inhaled antimicrobial prophylaxis to prevent VAP in mechanically ventilated ICU patients?
Primary Objective:
To assess the feasibility of conducting a full-scale randomized controlled trial, including protocol adherence, timely microbiome result reporting, and timely initiation and completion of the assigned intervention, and safety.
Secondary Objectives:
To explore the impact of microbiome-guided inhaled prophylaxis on airway microbiome composition and to estimate clinical outcomes including VAP incidence, ventilator-free days, ICU and hospital length of stay, and mortality up to 28 days.
Hypothesis:
Microbiome-guided inhaled antimicrobial prophylaxis is feasible and may be superior to standard care in reducing airway pathogen burden and VAP incidence.
Methods:
This is a single-centre, randomized, placebo-controlled pilot trial enrolling 70 mechanically ventilated adult ICU patients at Foothills Medical Centre in Calgary, AB, Canada. Participants will be randomized 1:1 to microbiome-guided inhaled antibiotic prophylaxis (intervention arm) or matching placebo (control arm). Endotracheal aspirates (ETA) will be collected at enrolment for rapid microbiome sequencing and analysis. In the intervention arm, participants with airway microbiome positive for VAP pathogens will receive inhaled tobramycin, participants with airway S. aureus will receive inhaled vancomycin, while those without pathogens will receive inhaled saline placebo. Treatment responsiveness will be determined on day 3 with repeat airway microbiome sequencing and analysis, and in participants with persistent airway pathogens, inhaled tobramycin will be changed to inhaled aztreonam, while those with airway S. aureus will continue to receive inhaled vancomycin. Total duration of intervention will be 5 days. Participants randomized to control arm, will undergo identical ETA sampling for airway microbiome sequencing but results will remain blinded, and participants will receive inhaled saline placebo for 5 days. Clinicians and participants will be blinded to microbiome results and allocation. Participants will be followed for up to 28 days for primary feasibility and safety outcomes (see section below for additional details), as well as secondary clinical outcomes and biological outcomes (airway microbiome and immune analyses).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Microbiome-guided inhaled antibiotic prophylaxis | Experimental | Drug: Microbiome-guided inhaled antibiotic prophylaxisParticipants randomized to "microbiome-guided antibiotic prophylaxis" will be administered inhaled antibiotics tailored to their airway microbiome composition. |
| Placebo control | Placebo comparator | Drug: PlaceboParticipants randomized to "placebo control" will be administered inhaled 0.9% saline placebo. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Microbiome-guided inhaled antibiotic prophylaxisParticipants 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. | Drug | Microbiome-guided inhaled antibiotic prophylaxis |
| PlaceboParticipants randomized to "placebo control" arm will receive inhaled placebo twice daily for 5 days. | Drug | Placebo control |
Primary outcome
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.
Time frame: ICU admission to hour 36.
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.
Safety: As defined by proportion of participants who develop treatment-emergent adverse events (TEAE) related to inhaled antimicrobials (or placebo).
Time frame: Enrolment to day 7
Proportion of participants who develop treatment-emergent adverse events (TEAE) related to inhaled antimicrobials (or placebo).
11 secondary outcomes
Ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP)
Time frame: Enrolment to day 28
All-cause mortality
Time frame: Enrolment to day 28
VAP/HAP-free survival
Time frame: Enrolment to day 28
Ventilator-free day
Time frame: Enrolment to day 28
ICU-free and hospital-free days
Time frame: Enrolment to day 28
Extubation failure
Time frame: Enrolment to day 28
Ventilator-associated complications and infection-related ventilator-associated complications
Time frame: Enrolment to day 28
Non-pneumonia hospital-acquired infections (HAIs)
Time frame: Enrolment to day 28
Illness severity
Time frame: Enrolment to day 28
Lung injury severity
Time frame: Enrolment to day 28
Additional safety outcomes
Time frame: Enrolment to day 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Microbiome-guided inhaled antibiotic prophylaxis in people with Critical Illness and Mechanical Ventilation, run by University of Calgary.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 11 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Braedon McDonald, MD, PhD, FRCPC (403-220-6885, bamcdona@ucalgary.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: ICU admission to hour 36.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2026.