LIGHTNING: HAP/VAP Diagnosis in Critically Ill Septic Patients Using a Multiplex PCR Array
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Film-array Pneumonia Panel Plus group Patients with suspected HAP or VAP in which lower tract respiratory samples are analyzed with new multiplex PCR assay (Film-array Pneumonia Panel Plus) |
Procedure: Lower 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 Test: Multiplex PCR assay (Film-array Pneumonia Panel Plus)
The lower tract respiratory samples will be analyzed with Multiplex PCR assay (Film-array Pneumonia Plus).
Diagnostic Test: Lower 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 Test: Blood sample standard culture
When HAP or VAP are suspected, blood samples from peripheral vein will be collected and analyzed with conventional microbiological methods
|
| Active Comparator: Standard culture group (control group) Patients with suspected HAP or VAP in which lower tract respiratory samples are analyzed with standard culture |
Procedure: Lower 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 Test: Lower 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 Test: Blood sample standard culture
When HAP or VAP are suspected, blood samples from peripheral vein will be collected and analyzed with conventional microbiological methods
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Suspicion of HAP/VAP (clinical/radiological/laboratory criteria);
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Availability to perform tracheal aspirates or broncoalveolar lavage within 1 hour from clinical suspicion
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Life expectancy ≥ 48 hours
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Signed written informed consent.
Exclusion Criteria:
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Pregnancy,
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Concomitant participating in other interventional trial
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Refusal to sign informed consent
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | S. Orsola Research Hospital | Bologna | Italy | ||
| 2 | Ospedale Careggi | Firenze | Italy | ||
| 3 | Modena Policlinico | Modena | Italy | ||
| 4 | Fondazione Policlinico Universitario "A. GEMELLI" IRCCS | Roma | Italy | 00168 |
Sponsors and Collaborators
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Catholic University of the Sacred Heart
Investigators
- Principal Investigator: Gennaro De Pascale, MD, Fondazione Policlinico A. Gemelli IRCCS
- Study Chair: Massimo Antonelli, MD, Fondazione Policlinico A. Gemelli IRCCS
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 5768