Mechanical VentilationPULMIVAPNCT04849039
Lung Microbiota and VAP Development (PULMIVAP)
An observational study of Mechanical Ventilation, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
Trial summary
Ventilator-associated pneumonia (VAP) refers to a lower respiratory tract nosocomial infection acquired >48h after being intubated in Intensive Care Units. Pathogenesis of VAP is mechanical and associated with microaspiration and leakage of oropharyngeal secretions around the endotracheal tube. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mechanical Ventilation
- How many people
- 700 participants
- Where
- 1 siteItaly
- Study dates
- 10 Sep 2020to 1 Jan 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: All adult patients mechanicaly ventilated for non pulmonary conditions
Who may be able to join
- Older than 18 years
- Patients ventilated for reasons other than pulmonary failure with an expected need for MV longer than 48 hours
Who cannot join
- Admission in ICU with a pneumonia
- Clinical Pulmonary Infectious Score (CPIS) > 6
- Antibiotic therapy > 3 days prior to the start of MV
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Fondazione Irccs Ca' Granda, Ospedale Maggiore Policlinico
Milan, MI, 20112
LAURA ALAGNA, Doctor, 02.5503.4770, laura.alagna@policlinico.mi.it
ANDREA GORI, Professor, 02.5503.4763, andrea.gori@unimi.it
About this study
Official title: "Pulmonary Microbiota and Related Immunity Role in Predicting Ventilator Associated- Pneumonia (VAP) Development in Mechanical Ventilated Patients"
Ventilator-associated pneumonia (VAP) refers to a lower respiratory tract nosocomial infection acquired >48h after being intubated in Intensive Care Units. Pathogenesis of VAP is mechanical and associated with microaspiration and leakage of oropharyngeal secretions around the endotracheal tube. A novel approach to VAP will attempt to explore how the abrupt ecological order of acute infection (high bacterial biomass, low community diversity) emerges from the dynamic homeostasis of a pre-existing ecosystem in which lung microbiota and local immunity interaction play their essential role.
Therefore, the investigators aim to explore if oral and lung microbiota modifications with local immunity changes, contribute in the pathogenesis of VAP in patients intubated for non-pulmonary reasons. Early changes in the host microbiota with the innate immunity system impairs tissue homeostasis and may represent a new distinct condition and a potential tool for early diagnosis and prevention of VAP.
Read the detailed description
Several factors are involved in the pathogenesis of VAP: the presence of endotracheal tube, the creation of bacterial biofilms around the device, host characteristics (comorbidities, surgery, antibiotic exposure) and, finally, immunological factors (including modulation of cytokine expression). In this study, patients mechanically ventilated for non-pulmonary reasons, will be followed up to 15 days of ventilation, estubation or death (whichever comes first). For microbiota analysis, all patients who develop VAP in the first 15 days of MV will be selected and matched (1:1; by center, gender, age (+/- 10 years), reason for intubation, duration of intubation), with a patient who do not developed VAP during MV. The optimal matching algorithm will be used to identify the control group that minimizes the total intra-pair dissimilarity.
The investigators plan to enroll about 700 MV patients for non-pulmonary conditions in order to describe VAP and non-VAP patients' characteristics identify. The investigators estimate that at least 70 patients will develop VAP in the first 15 days of MV. Microbiota and immunological analysis will be longitudinally performed on tracheal aspirate samples and oro-pharyngeal swab. The investigators will performe microbiota analyses on tracheal aspirate and oropharyngeal swab according to the following time schedule:
- VAP patient, 3 times: intubation (T0), the 24h before VAP development (T pre-VAP) and at VAP development (T-VAP).
- non-VAP patient, 2 times: intubation (T0) and a second sample, selected at the time point (day), corresponding to T-VAP of his/her matched VAP-patient (T no-VAP).
The investigators will perform immunological analysis on tracheal aspirate for all patients at intubation and at T-VAP or T no-VAP time.
- Conditions
- Mechanical Ventilation
- Keywords
- Observational, Cohort Study, Ventilator-associated pneumonia, Mechanical Ventilation, Lung microbiota
- Medical subject headings
- Pneumonia, Ventilator-Associated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Mechanicaly ventilated adult patients for non-pulmonary conditions | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lung/oral microbiota and VAP development
Alfa and beta diversity variation based on 16S-rRNA sequencing in tracheal aspirates and oral samples.
To explore the association between the composition and related changes over time of the lung/oral microbiota and VAP development has been used the measure of the alfa-diversity (number of different OTUs in each sample) and beta-diversity (similarity between samples in terms of OTUS composition).
Measured: (Time frame for VAP patients: intubation (T0), 24h before VAP development (T pre- VAP) and at VAP development (T-VAP). Time frame for non-VAP patients: intubation (T0), samples corresponding to T-VAP of matched VAP patients (T no VAP))
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2021
- Study start10 Sep 2020
- Primary completion1 Nov 2022 (estimated)
- Study completion1 Jan 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Mechanical VentilationStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
- Sponsor type
- University, hospital or other
- Collaborators
- San Gerardo Hospital, University of Parma
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04849039
- Sponsor's protocol ID
- 1469-23.07.2019
- Acronym
- PULMIVAP
- Status last verified
- Feb 2021
- First submitted
- 24 Feb 2021
- Last updated
- 19 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Spalding MC, Cripps MW, Minshall CT. Ventilator-Associated Pneumonia: New Definitions. Crit Care Clin. 2017 Apr;33(2):277-292. doi: 10.1016/j.ccc.2016.12.009. Epub 2017 Jan 18.
PubMed 28284295Emonet S, Lazarevic V, Leemann Refondini C, Gaia N, Leo S, Girard M, Nocquet Boyer V, Wozniak H, Despres L, Renzi G, Mostaguir K, Dupuis Lozeron E, Schrenzel J, Pugin J. Identification of respiratory microbiota markers in ventilator-associated pneumonia. Intensive Care Med. 2019 Aug;45(8):1082-1092. doi: 10.1007/s00134-019-05660-8. Epub 2019 Jun 17.
PubMed 31209523Zakharkina T, Martin-Loeches I, Matamoros S, Povoa P, Torres A, Kastelijn JB, Hofstra JJ, de Wever B, de Jong M, Schultz MJ, Sterk PJ, Artigas A, Bos LDJ. The dynamics of the pulmonary microbiome during mechanical ventilation in the intensive care unit and the association with occurrence of pneumonia. Thorax. 2017 Sep;72(9):803-810. doi: 10.1136/thoraxjnl-2016-209158. Epub 2017 Jan 18.
PubMed 28100714Shimizu T, Kono M, Watanabe H, Adachi S, Hasegawa M, Okuda K, Tanaka K, Kameda K, Hirota S, Sako M. [CT evaluation in the diagnosis of pulmonary nodules using lung phantom]. Nihon Igaku Hoshasen Gakkai Zasshi. 1987 Oct 25;47(10):1251-9. No abstract available. Japanese.
PubMed 3441423Martin-Loeches I, Dickson R, Torres A, Hanberger H, Lipman J, Antonelli M, de Pascale G, Bozza F, Vincent JL, Murthy S, Bauer M, Marshall J, Cilloniz C, Bos LD. The importance of airway and lung microbiome in the critically ill. Crit Care. 2020 Aug 31;24(1):537. doi: 10.1186/s13054-020-03219-4.
PubMed 32867808Yatera K, Mukae H. Drastic change in the lung microbiome induced by mechanical ventilation. Respir Investig. 2020 Nov;58(6):425-426. doi: 10.1016/j.resinv.2020.07.005. Epub 2020 Sep 3. No abstract available.
PubMed 32893161Sommerstein R, Merz TM, Berger S, Kraemer JG, Marschall J, Hilty M. Patterns in the longitudinal oropharyngeal microbiome evolution related to ventilator-associated pneumonia. Antimicrob Resist Infect Control. 2019 May 22;8:81. doi: 10.1186/s13756-019-0530-6. eCollection 2019.
PubMed 31139364Dickson RP, Schultz MJ, van der Poll T, Schouten LR, Falkowski NR, Luth JE, Sjoding MW, Brown CA, Chanderraj R, Huffnagle GB, Bos LDJ; Biomarker Analysis in Septic ICU Patients (BASIC) Consortium. Lung Microbiota Predict Clinical Outcomes in Critically Ill Patients. Am J Respir Crit Care Med. 2020 Mar 1;201(5):555-563. doi: 10.1164/rccm.201907-1487OC.
PubMed 31973575Huebinger RM, Smith AD, Zhang Y, Monson NL, Ireland SJ, Barber RC, Kubasiak JC, Minshall CT, Minei JP, Wolf SE, Allen MS. Variations of the lung microbiome and immune response in mechanically ventilated surgical patients. PLoS One. 2018 Oct 24;13(10):e0205788. doi: 10.1371/journal.pone.0205788. eCollection 2018.
PubMed 30356313Yin Y, Hountras P, Wunderink RG. The microbiome in mechanically ventilated patients. Curr Opin Infect Dis. 2017 Apr;30(2):208-213. doi: 10.1097/QCO.0000000000000352.
PubMed 28067677Mancabelli L, Palomba E, Magni F, Chatenoud L, Olgiati I, Buracchi C, Bugarin C, Gaipa G, Abbruzzese C, Filippini M, Forastieri A, Fumagalli R, Geraldini F, Picetti E, Terranova L, Vaschetto R, Zoerle T, Ventura M, Citerio G, Gori A, Bandera A, Alagna L, Turroni F. Microbial signatures and host immune responses associated with the development of ventilator-associated pneumonia among patients with neurological injuries. Microbiol Spectr. 2026 Mar 23;14(5):e0319325. doi: 10.1128/spectrum.03193-25. Online ahead of print.
PubMed 41869813
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "Pulmonary Microbiota and Related Immunity Role in Predicting Ventilator Associated- Pneumonia (VAP) Development in Mechanical Ventilated Patients"
- ClinicalTrials.gov ID
- NCT04849039
- Acronym / sponsor ID
- PULMIVAP / 1469-23.07.2019
- Conditions
- Mechanical Ventilation
- Keywords
- Observational, Cohort Study, Ventilator-associated pneumonia, Mechanical Ventilation, Lung microbiota
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 700 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoUniversity, hospital or other
- Collaborators
- San Gerardo Hospital, University of Parma
- Study start
- 10 Sep 2020 (actual)
- Primary completion
- 1 Nov 2022 (estimated)
- Study completion
- 1 Jan 2023 (estimated)
- First posted
- 19 Apr 2021 (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) refers to a lower respiratory tract nosocomial infection acquired >48h after being intubated in Intensive Care Units. Pathogenesis of VAP is mechanical and associated with microaspiration and leakage of oropharyngeal secretions around the endotracheal tube. A novel approach to VAP will attempt to explore how the abrupt ecological order of acute infection (high bacterial biomass, low community diversity) emerges from the dynamic homeostasis of a pre-existing ecosystem in which lung microbiota and local immunity interaction play their essential role.
Therefore, the investigators aim to explore if oral and lung microbiota modifications with local immunity changes, contribute in the pathogenesis of VAP in patients intubated for non-pulmonary reasons. Early changes in the host microbiota with the innate immunity system impairs tissue homeostasis and may represent a new distinct condition and a potential tool for early diagnosis and prevention of VAP.
Detailed description
Several factors are involved in the pathogenesis of VAP: the presence of endotracheal tube, the creation of bacterial biofilms around the device, host characteristics (comorbidities, surgery, antibiotic exposure) and, finally, immunological factors (including modulation of cytokine expression). In this study, patients mechanically ventilated for non-pulmonary reasons, will be followed up to 15 days of ventilation, estubation or death (whichever comes first). For microbiota analysis, all patients who develop VAP in the first 15 days of MV will be selected and matched (1:1; by center, gender, age (+/- 10 years), reason for intubation, duration of intubation), with a patient who do not developed VAP during MV. The optimal matching algorithm will be used to identify the control group that minimizes the total intra-pair dissimilarity.
The investigators plan to enroll about 700 MV patients for non-pulmonary conditions in order to describe VAP and non-VAP patients' characteristics identify. The investigators estimate that at least 70 patients will develop VAP in the first 15 days of MV. Microbiota and immunological analysis will be longitudinally performed on tracheal aspirate samples and oro-pharyngeal swab. The investigators will performe microbiota analyses on tracheal aspirate and oropharyngeal swab according to the following time schedule:
- VAP patient, 3 times: intubation (T0), the 24h before VAP development (T pre-VAP) and at VAP development (T-VAP).
- non-VAP patient, 2 times: intubation (T0) and a second sample, selected at the time point (day), corresponding to T-VAP of his/her matched VAP-patient (T no-VAP).
The investigators will perform immunological analysis on tracheal aspirate for all patients at intubation and at T-VAP or T no-VAP time.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mechanicaly ventilated adult patients for non-pulmonary conditions | – | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All adult patients mechanicaly ventilated for non pulmonary conditions
Key inclusion criteria (2 listed)
- Older than 18 years
- Patients ventilated for reasons other than pulmonary failure with an expected need for MV longer than 48 hours
Key exclusion criteria (3 listed)
- Admission in ICU with a pneumonia
- Clinical Pulmonary Infectious Score (CPIS) > 6
- Antibiotic therapy > 3 days prior to the start of MV
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Lung/oral microbiota and VAP development
Time frame: (Time frame for VAP patients: intubation (T0), 24h before VAP development (T pre- VAP) and at VAP development (T-VAP). Time frame for non-VAP patients: intubation (T0), samples corresponding to T-VAP of matched VAP patients (T no VAP))
Alfa and beta diversity variation based on 16S-rRNA sequencing in tracheal aspirates and oral samples. To explore the association between the composition and related changes over time of the lung/oral microbiota and VAP development has been used the measure of the alfa-diversity (number of different OTUs in each sample) and beta-diversity (similarity between samples in terms of OTUS composition).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2021.
- Background: PubMed 28284295Spalding MC, Cripps MW, Minshall CT. Ventilator-Associated Pneumonia: New Definitions. Crit Care Clin. 2017 Apr;33(2):277-292. doi: 10.1016/j.ccc.2016.12.009. Epub 2017 Jan 18.
- Background: PubMed 31209523Emonet S, Lazarevic V, Leemann Refondini C, Gaia N, Leo S, Girard M, Nocquet Boyer V, Wozniak H, Despres L, Renzi G, Mostaguir K, Dupuis Lozeron E, Schrenzel J, Pugin J. Identification of respiratory microbiota markers in ventilator-associated pneumonia. Intensive Care Med. 2019 Aug;45(8):1082-1092. doi: 10.1007/s00134-019-05660-8. Epub 2019 Jun 17.
- Background: PubMed 28100714Zakharkina T, Martin-Loeches I, Matamoros S, Povoa P, Torres A, Kastelijn JB, Hofstra JJ, de Wever B, de Jong M, Schultz MJ, Sterk PJ, Artigas A, Bos LDJ. The dynamics of the pulmonary microbiome during mechanical ventilation in the intensive care unit and the association with occurrence of pneumonia. Thorax. 2017 Sep;72(9):803-810. doi: 10.1136/thoraxjnl-2016-209158. Epub 2017 Jan 18.
- Background: PubMed 3441423Shimizu T, Kono M, Watanabe H, Adachi S, Hasegawa M, Okuda K, Tanaka K, Kameda K, Hirota S, Sako M. [CT evaluation in the diagnosis of pulmonary nodules using lung phantom]. Nihon Igaku Hoshasen Gakkai Zasshi. 1987 Oct 25;47(10):1251-9. No abstract available. Japanese.
- Background: PubMed 32867808Martin-Loeches I, Dickson R, Torres A, Hanberger H, Lipman J, Antonelli M, de Pascale G, Bozza F, Vincent JL, Murthy S, Bauer M, Marshall J, Cilloniz C, Bos LD. The importance of airway and lung microbiome in the critically ill. Crit Care. 2020 Aug 31;24(1):537. doi: 10.1186/s13054-020-03219-4.
- Background: PubMed 32893161Yatera K, Mukae H. Drastic change in the lung microbiome induced by mechanical ventilation. Respir Investig. 2020 Nov;58(6):425-426. doi: 10.1016/j.resinv.2020.07.005. Epub 2020 Sep 3. No abstract available.
- Background: PubMed 31139364Sommerstein R, Merz TM, Berger S, Kraemer JG, Marschall J, Hilty M. Patterns in the longitudinal oropharyngeal microbiome evolution related to ventilator-associated pneumonia. Antimicrob Resist Infect Control. 2019 May 22;8:81. doi: 10.1186/s13756-019-0530-6. eCollection 2019.
- Background: PubMed 31973575Dickson RP, Schultz MJ, van der Poll T, Schouten LR, Falkowski NR, Luth JE, Sjoding MW, Brown CA, Chanderraj R, Huffnagle GB, Bos LDJ; Biomarker Analysis in Septic ICU Patients (BASIC) Consortium. Lung Microbiota Predict Clinical Outcomes in Critically Ill Patients. Am J Respir Crit Care Med. 2020 Mar 1;201(5):555-563. doi: 10.1164/rccm.201907-1487OC.
- Background: PubMed 30356313Huebinger RM, Smith AD, Zhang Y, Monson NL, Ireland SJ, Barber RC, Kubasiak JC, Minshall CT, Minei JP, Wolf SE, Allen MS. Variations of the lung microbiome and immune response in mechanically ventilated surgical patients. PLoS One. 2018 Oct 24;13(10):e0205788. doi: 10.1371/journal.pone.0205788. eCollection 2018.
- Background: PubMed 28067677Yin Y, Hountras P, Wunderink RG. The microbiome in mechanically ventilated patients. Curr Opin Infect Dis. 2017 Apr;30(2):208-213. doi: 10.1097/QCO.0000000000000352.
- Derived from this study: PubMed 41869813Mancabelli L, Palomba E, Magni F, Chatenoud L, Olgiati I, Buracchi C, Bugarin C, Gaipa G, Abbruzzese C, Filippini M, Forastieri A, Fumagalli R, Geraldini F, Picetti E, Terranova L, Vaschetto R, Zoerle T, Ventura M, Citerio G, Gori A, Bandera A, Alagna L, Turroni F. Microbial signatures and host immune responses associated with the development of ventilator-associated pneumonia among patients with neurological injuries. Microbiol Spectr. 2026 Mar 23;14(5):e0319325. doi: 10.1128/spectrum.03193-25. Online ahead of print.
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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. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mechanical Ventilation, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
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 2 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 19 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Laura Alagna, Doctor (02.5503.4770, laura.alagna@policlinico.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lung/oral microbiota and VAP development (time frame: (Time frame for VAP patients: intubation (T0), 24h before VAP development (T pre- VAP) and at VAP development (T-VAP). Time frame for non-VAP patients: intubation (T0), samples corresponding to T-VAP of matched VAP patients (T no VAP))). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04849039, which also lists 11 linked publications.
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 19 Apr 2021.