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Trial record 12 of 11681 for:    Anti-Infective Agents AND antibacterial

Impact of Direct Antimicrobial Susceptibility Testing on Respiratory Sample of Intensive Care Patient With Suspected VAP (AB-DIRECT2)

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ClinicalTrials.gov Identifier: NCT02897466
Recruitment Status : Recruiting
First Posted : September 13, 2016
Last Update Posted : October 15, 2018
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

Inappropriate antibiotic therapy in ventilator-associated pneumonia (VAP) is associated with increased mortality. The international guidelines recommend using broad spectrum antimicrobials especially in patients who received previous antimicrobials, with risk factors of muti-drug resistant (MDR) VAP or after 5 days of mechanical ventilation. Using broad-spectrum antibiotics for 48h until the results of conventional cultures and antimicrobial susceptibility testing (AST) are available, may promote the emergence of drug-resistant bacteria. Exposure to imipenem, as short as 1 to 3 days, is associated with a 5-fold increase in the risk of imipenem resistance in the gut microbiota of ICU patients (Armand-Lefevre AAC 2013). Performing AST directly on clinical respiratory samples would hasten the process by at least 24h.

The diagnostic performance of a rapid method combining mass spectrometry and direct AST [DAST] are previously analyzed, and compared it with the conventional method (mass spectrometry with conventional AST [CAST]) and its potential impact was assessed on antimicrobial use in 85 patients (Le DORZE M et al - Clin. Microbiol. Infect. 2015).

The results produced by the dast were useable in 85,9% of the cases and the sensitivity and negative predictive values of DAST were 100% for all antibiotics tested, except gentamicin (97.1% [95%CI = 93.3-101] and 97.4% [93.7-101], respectively) and amikacin (88.9% [81.7-96.1] and 96.4% [92.1-100.7], respectively), compared with CAST. Specificity and positive predictive values ranged from 82.9 (74.2-91.5) to 100%, and from 86.4 (78.5−94.2) to 100%, respectively. If results had been reported to the clinicians, that DAST would have saved carbapenem prescription in 17 cases (22%) and would have allowed immediate narrow spectrum antimicrobials in 35/85 (41.2%) cases. But, the benefit of DAST was based on a simulation and should be now tested in a randomized fashion. This project is a prospective multicenter study. The hypothesis is that, DAST compared to CAST, would increase the number of adequate antimicrobial therapy within 24 hours in case of late VAP (> 5 days under mechanical ventilation) with Gram negative bacilli (GNB) in IC patients while sparing carbapenems (imipenem and meropenem). The primary objective is to determine the impact of a strategy using DAST on the rate of day1 adequate therapy without carbapenems in case of late VAP due to GNB.


Condition or disease Intervention/treatment Phase
Ventilator-associated Pneumonia Other: Direct Antimicrobial Susceptibility Testing Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Other
Official Title: Impact of Susceptibility Testing Directly on the Deep Respiratory Samples of Patients Suspected Pneumonia Ventilator ( VAP ) Late ( > 5 Days) in Intensive Care Unit on the Adequacy of Antibiotic Treatment to Carbapenems Sparing on Day 1
Actual Study Start Date : December 11, 2017
Estimated Primary Completion Date : July 11, 2019
Estimated Study Completion Date : January 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Direct Antimicrobial Susceptibility Testing

At day 0: Direct antibiotic susceptibility testing performed directly (DAST) on the respiratory sample At day 1: both results of isolated GNB identification using mass spectrometry and DAST will be given to the physician in charge in order to switch antimicrobial therapy to an antibiotic with a spectrum as narrow as possible with the main objective to avoid whenever possible carbapenems. Conventional antibiotic susceptibility testing (CAST) performed on isolated GNB.

At day 2-3: results of CAST will be given to the physician in charge in order to change antimicrobial therapy in case of differences between CAST and DAST (2nd switch to an antibiotic with a spectrum as narrow as possible with the main objective to avoid whenever possible carbapenems)

Other: Direct Antimicrobial Susceptibility Testing
An antibiotic susceptibility testing will be performed directly on respiratory samples with Gram negative bacilli on direct smear examination of intensive care patients suspected of ventilator-associated pneumonia. The result of this test associated with GNB identification using mass spectrometry will be given to the physician in charge of the patient at Day 1, one day earlier than the conventional AST. This rapid method will allow a re-evaluation (adequation and/or de-escalation) of the antibiotic probabilist treatment one day earlier than the conventional method.
Other Name: DAST

No Intervention: Conventional Antimicrobial Susceptibility Testing

At day 1 identification of isolated GNB bacilli using mass spectrometry will be given to the physician in charge (usual care in ICU involved) to adapt antibiotic regimen. Conventional antibiotic susceptibility testing (CAST) performed on isolated GNB.

At day 2-3: results of CAST will be given to the physician in charge in order to switch antimicrobial therapy to an antibiotic with a spectrum as narrow as possible with the main objective to avoid whenever possible carbapenems.




Primary Outcome Measures :
  1. The proportion of patients with an adequate antimicrobial therapy without carbapenem (imipenem, meropenem) at Day 1 [ Time Frame: 2 days ]
    The proportion of patients with an adequate antimicrobial therapy without carbapenem (imipenem, meropenem) at Day 1


Secondary Outcome Measures :
  1. The proportion of patients with an adequate antimicrobial therapy at Day1 [ Time Frame: 2 days ]
    The proportion of patients with an adequate antimicrobial therapy at Day1

  2. The number of days alive without carbapenem between day 1 and day 28 [ Time Frame: 28 days ]
    The number of days alive without carbapenem between day 1 and day 28

  3. The number of days alive without a broad spectrum antibiotic therapy between day 1 and day 28 [ Time Frame: 28 days ]
    The number of days alive without a broad spectrum antibiotic therapy between day 1 and day 28

  4. The proportion of patients with a de-escalation at Day 1 according to previous definition (Weiss et al.) [ Time Frame: 2 day ]
    The proportion of patients with a de-escalation at Day 1 according to previous definition (Weiss et al.)

  5. The proportion of patients with a relapse or a new VAP occured between day 1 and day 28 [ Time Frame: 28 days ]
    The proportion of patients with a relapse or a new VAP occured between day 1 and day 28

  6. The proportion of patients with a multidrug-resistant bacteria isolated from clinical or screening samples between day 1 and day 28 [ Time Frame: 28 days ]
    The proportion of patients with a multidrug-resistant bacteria isolated from clinical or screening samples between day 1 and day 28

  7. Evolution of the CPIS score between day 1 and day 28 [ Time Frame: 28 days ]

    The Clinical Pulmonary Infection Score (CPIS) is calculated with the following parameters :

    • Temperature (Celsius)
    • White Blood Cell Count
    • Tracheal Secretions
    • PaO2/FiO2
    • Chest Radiograph

  8. Evolution of the PaO2/FiO2 ratio between day 1 and day 28 [ Time Frame: 28 days ]
    Evolution of the PaO2/FiO2 ratio between day 1 and day 28

  9. Evolution of the SOFA score between day 1 and day 28 [ Time Frame: 28 days ]

    The Sequential Organ Failure Assessment (SOFA) score is calculated with the combination of 6 scores.

    • respiratory score with the parameter PaO2/FiO2
    • neurological score with the Glasgow scale
    • cardiovascular score with Mean arterial pressure parameter
    • hepatic score with bilirubin parameter
    • coagulation score with measure of platelets
    • renal score with creatinine parameter

  10. The number of days alive without mechanical ventilation between day 1 and day 28 [ Time Frame: 28 days ]
    The number of days alive without mechanical ventilation between day 1 and day 28

  11. The length of ICU stay [ Time Frame: 28 days ]
    The length of ICU stay

  12. ICU-mortality at day 28 [ Time Frame: 28 days ]
    ICU-mortality at day 28

  13. The proportion of concordant antibiotic susceptibility results between DAST and CAST [ Time Frame: 2 days ]
    Accuracy of the DAST. Sensitivity, specificity, positive predictive value, negative predictive value

  14. Cost minimization because of the DAST strategy [ Time Frame: 2 days ]
    The consumed resources considered will be evaluated for each strategy



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults (18 years or older)
  • Need for mechanical ventilation expected for at least 5 days at any time during the ICU stay (including if the intubation was performed before the ICU admission)
  • VAP suspected and clinical respiratory samples with GNB at direct smear examination
  • At least one condition with a risk factor of multidrug resistant infection:

    1. Previous use of antimicrobials (at least 2 days in the past 7 days)
    2. Risk of colonization or infection with MDR or XDR bacteria within 3 months
  • Written informed consent has to be obtained from the patients or a surrogate. The patient or his surrogate can withdraw from the study at any time.

Exclusion Criteria:

  • Pregnant or lactating women
  • VAP suspected and respiratory samples without GNB at direct smear examination
  • VAP that occurred without neither previous antimicrobial exposure in the past 5 days or neither risk of MDR colonization
  • Samples send to the lab during night and weekend in center if respiratory samples are not performed during this period
  • Active therapeutic limitation
  • Known allergy to antibiotics
  • Social welfare unavailable

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02897466


Contacts
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Contact: Laurence ARMAND-LEFEVRE, MD 140258500 ext +33 laurence.armand@aphp.fr
Contact: Jean-François TIMSIT, Pr MD jean-francois.timsit@aphp.fr

Locations
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France
Bichat Hospital Recruiting
Paris, France, 75018
Contact: Laurence ARMAND-LEFEVRE, MD       laurence.armand@aphp.fr   
Contact: Lila BOUADMA, Pr MD       lila.bouadma@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Laurence ARMAND-LEFEVRE, MD Assistance Publique - Hôpitaux de Paris

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02897466     History of Changes
Other Study ID Numbers: P150926
AOR15086 ( Other Grant/Funding Number: FRENCH MINISTRY OF HEALTH )
First Posted: September 13, 2016    Key Record Dates
Last Update Posted: October 15, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
ventilator-associated pneumonia
Multidrug-resistant bacteria

Additional relevant MeSH terms:
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Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents
Pneumonia, Ventilator-Associated
Pneumonia
Disease Susceptibility
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Disease Attributes
Pathologic Processes
Cross Infection
Infection