Can we Better Understand the Development of VAP and Eventually Predict and Prevent it?

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University Hospital, Geneva
Sponsor:
Information provided by (Responsible Party):
Prof. Jacques SCHRENZEL, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01875692
First received: March 15, 2013
Last updated: May 23, 2014
Last verified: May 2014
  Purpose

Pathogens of ventilator-associated pneumonia (VAP) come from colonizers of the trachea. The hypothesis of the investigators is that during the first days of intubation, independently of the use of antibiotics, there is a change in the oro-pharyngeal flora leading to the selection of one pathogen in the trachea, that will finally be the cause of VAP.

The investigators designed a prospective study including 300 patients intubated for more than 3 days, with daily analysis of oro-pharyngeal juice and tracheal aspirate by culture and metagenomics, in order to determine if this microbiological surveillance permits:

  1. To predict a high risk to develop a VAP in the next 48h and even to predict its agent
  2. To better understand the development of VAP by studying the evolution of the "respiratory flora" in the context of intubation

Condition
Pneumonia, Ventilator-Associated

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Culture Versus Genomics: Study of Oropharyngeal and Tracheal Flora in Intubated Patients. Can we Better Understand the Development of Ventilator-Acquired Pneumonia (VAP) and Predict Its Causing Pathogen(s)?

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • Percentage of cases where tracheal (same for oropharyngeal) aspirate clearly showing a selection of the same pathogen retrieved later in the bronchoalveolar lavage (BAL), when VAP happens. [ Time Frame: After 18 months ] [ Designated as safety issue: No ]
    This will provide the sensitivity of tracheal culture to identify correctly the agent of VAP before VAP happens.

  • Percentage of case where the pathogen selected in tracheal (same for oropharyngeal) aspirate do not correspond to the agent of VAP as identified by BAL. [ Time Frame: After 18 months ] [ Designated as safety issue: No ]
    Helps to determine the "specificity" of tracheal aspirates to predict the agent of VAP.

  • Percentage of cases where despite the selection of only one pathogen in tracheal aspirate (same for oropharyngeal) aspirate, the patient did never suffer from VAP [ Time Frame: After 18 months ] [ Designated as safety issue: No ]
    Helps determining the positive and negative predictive values of tracheal aspirates to predict VAP.

  • Presence of Ventilator-Associated-Pneumonia (VAP) [ Time Frame: After 18 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of VAP in the study population [ Time Frame: After 18 months ] [ Designated as safety issue: No ]
  • Type of bacteria retrieved on intubation day compared to type of bacteria retrieved after 1 week of intubation [ Time Frame: After 18 months ] [ Designated as safety issue: No ]

    The investigators expect to find normal oropharyngeal flora on intubation day but Gram negative pathogens after one week, despite the absence of antibiotherapy.

    This will be compared with and without antibiotherapy.


  • Evolution of metagenomics of oropharyngeal - tracheal aspirates in cases (VAP) and control (no VAP) [ Time Frame: After 18 months ] [ Designated as safety issue: No ]
    For patients suffering from VAP, metagenomics will also be assessed in the BAL. This will give the investigators some clues on the "respiratory flora" equilibrium and its evolution in cases and control


Estimated Enrollment: 300
Study Start Date: October 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Detailed Description:

BACKGROUND OF THE STUDY:

The ventilator-associated pneumonia (VAP) is responsible for almost half of infections acquired in intensive care, affecting up to 28% of mechanically ventilated patients with a mortality rate ranging from 25 to 50%. The majority of these VAP originate in the sub-glottic juice that accumulates just above the endotracheal tube cuff. Many preventive measures exist and are applied in this institution, including oropharyngeal aspiration every 4 hours and tracheal aspirates every 8 hours. Currently, these aspirates are simply discarded. However, a French study evaluating the colonization and infection of the respiratory tract of patients with acute respiratory distress syndrome (ARDS) has highlighted that the causative agent of VAP is selected in more than 2/3 of the cases in tracheal aspirates several days before the VAP. This suggest that "microbiological surveillance" of daily aspirates may permit the identification of a selected respiratory pathogen later responsible of VAP.

Parallel to this, the rapid development of genomics has highlighted the role of flora (microbiota) and its link with disease (eg, colitis and intestinal microbiota inflammatory). This area is also emerging in the field of respiratory tract infections, for example in patients with chronic obstructive pulmonary disease (COPD) or asthma. There is no description yet of metagenomics changes in respiratory flora of patients intubated with or without VAP, neither evaluation of the benefits of such an approach in relation to classical microbiology. The investigators believe that studying the respiratory flora of ventilated patients could provide clues to better understand the development of VAP.

METHODOLOGY (plan, inclusion and objectives):

Prospective study of 300 intubated patients recruited during a period of 2 years, in whom tracheal aspirates and oropharyngeal juice collected daily will be analyzed by culture and metagenomics, instead of being simply discarded. The results of these analyzes will be used only for research purposes (culture and metagenomics in parallel).

The main objective is to determine whether daily monitoring of oropharyngeal juice and tracheal aspirates by culture identifies the selection of a pathogen among the colonizing flora, which would be predictive of the onset of VAP in 48-72 hours.

The secondary objectives are to obtain new knowledge on the kinetics of colonization and respiratory infections in intubated patients, compare the advantages and disadvantages of a metagenomic approach compared to culture in this context, and study the influence of antibiotherapy in this context.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

ICU adult patients intubated in the last 24h for a condition that will probably require more than 3 days of mechanical ventilation.

Criteria

Inclusion Criteria:

  • Patient hospitalised in the adult ICU of HUG (>18 years old)
  • Intubated for < 24 hours
  • Expected duration of intubation > 4 days (e.g. neurologic disease)

Exclusion Criteria:

  • Patients for whom regular tracheal aspirations cannot not be performed (because of unstable intracranial pressure, for example).
  • New antibiotic therapy in the week preceding the intubation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01875692

Contacts
Contact: Stephane P Emonet, MD +41223727323 stephane.emonet@hcuge.ch

Locations
Switzerland
University Hospital Recruiting
Geneva, Switzerland, 1201
Contact: Stephane P Emonet, MD    +41223727323    stephane.emonet@hcuge.ch   
Sub-Investigator: Stephane P Emonet, MD         
Principal Investigator: Jacques Schrenzel, Prof.         
Sponsors and Collaborators
University Hospital, Geneva
Investigators
Principal Investigator: Jacques Schrenzel, Prof. University Hospitals Geneva
  More Information

No publications provided

Responsible Party: Prof. Jacques SCHRENZEL, Professor, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT01875692     History of Changes
Other Study ID Numbers: 12-051
Study First Received: March 15, 2013
Last Updated: May 23, 2014
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Geneva:
Metagenomic
Ventilator-Associated Pneumonia (VAP)

Additional relevant MeSH terms:
Pneumonia
Pneumonia, Ventilator-Associated
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Cross Infection
Infection
Ventilator-Induced Lung Injury
Lung Injury

ClinicalTrials.gov processed this record on August 18, 2014