HAP - Hospital Acquired Pneumonia, VAP - Ventilator Associated Pneumonia
Conditions
Brief summary
Multicenter, randomized, controlled, open-label trial to assess if semiquantitative multiplex PCR assay, as compared to conventional microbiology, can reduce the percentage of patients without microbiological diagnosis in the first 24 hours from HAP/VAP suspicion, thus allowing early de-escalation.
Detailed description
Hospital-acquired pneumonia and ventilator-associated pneumonia are leading cause of morbidity and mortality in Intensive Care Unit due to the underlining clinical conditions of critically ill patients and the high rate of multidrug resistance among causative agents. In patients with sepsis and septic shock, early and appropriate antibiotics are essential for improving clinical outcome, often requiring the use of broad-spectrum combinations. The optimal use of antimicrobials is part of current implementation programs aimed to reduce the administration of not-necessary antibiotics, the bio-ecologic pressure and the possible side effects . In this context the application of rapid, molecular microbiological tests on respiratory samples is of overwhelming interest, due to the potential of reducing the time to inappropriate antibiotic therapy and of prompting de-escalation. During last years a new Multiplex PCR Assay for pneumonia diagnosis (Film-Array Pneumonia Panel Plus, BioFire, Salt Lake City, UT, USA) has been implementing in the clinical practice, showing very high rates of negative and positive predictive values. The hypothesis is that molecular test on lower respiratory tract samples may reduce the time to microbiological diagnosis, thus allowing early antibiotic de-escalation.
Interventions
PROCEDURELower tract respiratory samples
Within 1 hour from HAP or VAP suspicion, quantitative tracheal aspirate or bronchoalveolar lavage will be performed to confirm the diagnosis. Clinicians will be encouraged to perform BAL whenever possible
DIAGNOSTIC_TESTMultiplex PCR assay (Film-array Pneumonia Panel Plus)
The lower tract respiratory samples will be analyzed with Multiplex PCR assay (Film-array Pneumonia Plus).
DIAGNOSTIC_TESTLower respiratory tract standard culture
The lower tract respiratory samples will be analyzed using convention microbiological methods (including conventional Gram stain and semiquantitative culture on both selective/differential and screening agar media)
DIAGNOSTIC_TESTBlood sample standard culture
When HAP or VAP are suspected, blood samples from peripheral vein will be collected and analyzed with conventional microbiological methods
Sponsors
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Catholic University of the Sacred Heart
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Randomized controlled, multicenter, open-label trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Suspicion of HAP/VAP (clinical/radiological/laboratory criteria); * Availability to perform tracheal aspirates or broncoalveolar lavage within 1 hour from clinical suspicion * Life expectancy ≥ 48 hours * Signed written informed consent.
Exclusion criteria
* Pregnancy, * Concomitant participating in other interventional trial * Refusal to sign informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients without microbiological diagnosis of HAP/VAP within the first 24 hours | 24 hours | Proportion of patients where a microbiological diagnosis of HAP/VAP is not avaiable within the first 24 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of antibiotic de-escalation as a consequence of microbiological results | 4 days | Proportion of patients in which antibiotic therapy has been modified from broad-spectrum empirical to targeted, due to microbiological results |
| Time to antibiotic de-escalation and optimal therapy | 4 days | Period of time from empirical antibiotic therapy initiation to modification due to microbiological results |
| Mechanical Ventilation free-days | 14 and 28 days | Number of days from enrollment in which the patients is not mechanically ventilated |
| Rate of MDR infection | 28 days | Proportion of patients who suffered from infection caused by multidrug resistant germ |
| Lenght of intensive care unit stay | 60 days | Period of time from enrollment in which the patient is admitted to the intensive care unit |
| Lenght of hospital stay | 60 days | Period of time from enrollment in which the patient is admitted to the hospital |
| In-Intensive care unit mortality | 28 days and 60 days | All-cause mortality, assessed during ICU stay |
| 28 days and 60 days mortality | 28 days and 60 days | All-cause mortality |
| SOFA score | 14 days | Measured SOFA score after 2,3,7 and 14 days from enrollment |
| Diagnostic concordance | 4 days | Proportion of patients in the interventional group, in which microbiological diagnosis is concordant when assessed with PCR array and standard culture |
| Adverse event | 28 days | Proportion of patients in which any adverse event is registered |
| In-Hospital mortality | 28 days and 60 days | All-cause mortality, assessed during Hospital stay |
Countries
Italy
Contacts
PRINCIPAL_INVESTIGATORGennaro De Pascale, MD
Fondazione Policlinico A. Gemelli IRCCS
STUDY_CHAIRMassimo Antonelli, MD
Fondazione Policlinico A. Gemelli IRCCS
Outcome results
None listed