Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04849039
Other study ID # 1469-23.07.2019
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date September 10, 2020
Est. completion date January 1, 2023

Study information

Verified date February 2021
Source Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Contact Laura Alagna, Doctor
Phone 02.5503.4770
Email laura.alagna@policlinico.mi.it
Is FDA regulated No
Health authority
Study type Observational

Clinical 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. 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 700
Est. completion date January 1, 2023
Est. primary completion date November 1, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Older than 18 years - Patients ventilated for reasons other than pulmonary failure with an expected need for MV longer than 48 hours Exclusion Criteria: - Admission in ICU with a pneumonia - Clinical Pulmonary Infectious Score (CPIS) > 6 - Antibiotic therapy > 3 days prior to the start of MV

Study Design


Locations

Country Name City State
Italy Fondazione Irccs Ca' Granda, Ospedale Maggiore Policlinico Milan MI

Sponsors (3)

Lead Sponsor Collaborator
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico San Gerardo Hospital, University of Parma

Country where clinical trial is conducted

Italy, 

References & Publications (10)

Dickson 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. — View Citation

Emonet S, Lazarevic V, Leemann Refondini C, Gaïa N, Leo S, Girard M, Nocquet Boyer V, Wozniak H, Després 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. — View Citation

Huebinger 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. — View Citation

Martin-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. Review. — View Citation

Shimizu 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. Japanese. — View Citation

Sommerstein 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. — View Citation

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. Review. — View Citation

Yatera K, Mukae H. Drastic change in the lung microbiome induced by mechanical ventilation. Respir Investig. 2020 Sep 3. pii: S2212-5345(20)30116-7. doi: 10.1016/j.resinv.2020.07.005. [Epub ahead of print] — View Citation

Yin 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. Review. — View Citation

Zakharkina 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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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).
(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))
See also
  Status Clinical Trial Phase
Completed NCT05921656 - Construction and Evaluation of Airway Leakage Risk Model of Patients With Endotracheal Tube
Recruiting NCT03941002 - Continuous Evaluation of Diaphragm Function N/A
Withdrawn NCT04288076 - The Brain and Lung Interaction (BALI) Study N/A
Completed NCT03031860 - Semi-quantitative Cough Strength Score (SCSS) N/A
Completed NCT02312869 - Local Assessment of Management of Burn Patients N/A
Completed NCT02545621 - A Role for RAGE/TXNIP/Inflammasome Axis in Alveolar Macrophage Activation During ARDS (RIAMA): a Proof-of-concept Clinical Study
Completed NCT01885442 - TryCYCLE: A Pilot Study of Early In-bed Leg Cycle Ergometry in Mechanically Ventilated Patients N/A
Completed NCT01204281 - Proportional Assist Ventilation (PAV) in Early Stage of Critically Ill Patients Phase 4
Terminated NCT01059929 - Dexmedetomidine Versus Propofol in the Medical Intensive Care Unit (MICU) Phase 4
Completed NCT00824239 - Intermittent Sedation Versus Daily Interruption of Sedation in Mechanically Ventilated Patients Phase 3
Completed NCT00529347 - Mechanical Ventilation Controlled by the Electrical Activity of the Patient's Diaphragm - Effects of Changes in Ventilator Parameters on Breathing Pattern Phase 1
Unknown status NCT00260676 - Protective Ventilatory Strategy in Potential Organ Donors Phase 3
Terminated NCT00205517 - Sedation and Psychopharmacology in Critical Care N/A
Completed NCT03281785 - Ultrasound of Diaphragmatic Musculature in Mechanically Ventilated Patients. N/A
Recruiting NCT04110613 - RCT: Early Feeding After PEG Placement N/A
Completed NCT04410783 - The Emergency Department Sedation Pilot Trial N/A
Recruiting NCT04821453 - NAVA vs. CMV Crossover in Severe BPD N/A
Completed NCT03930147 - Ventilation With ASV Mode in Children N/A
Recruiting NCT05029167 - REstrictive Versus LIberal Oxygen Strategy and Its Effect on Pulmonary Hypertension After Out-of-hospital Cardiac Arrest (RELIEPH-study) N/A
Recruiting NCT06006208 - AMBU Bag Manual Ventilation vs. Transport Ventilator Mechanical Ventilation for Transport N/A