HAP/VAP Diagnosis in Critically Ill Septic Patients Using a Multiplex PCR Array

Study Overview
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Brief Summary
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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
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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.

Official Title
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HAP/VAP Diagnosis in Critically Ill Septic Patients Using a Multiplex PCR Assay: A Multicenter Randomized Open-Label Trial. THE LIGHTNING STUDY

Conditions
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HAP - Hospital Acquired Pneumonia, VAP - Ventilator Associated Pneumonia

Intervention / Treatment
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* Procedure: Lower tract respiratory samples
* Diagnostic Test: Multiplex PCR assay (Film-array Pneumonia Panel Plus)
* Diagnostic Test: Lower respiratory tract standard culture
* Diagnostic Test: Blood sample standard culture


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled, multicenter, open-label trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Film-array Pneumonia Panel Plus group<br>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<br>* 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<br>Diagnostic Test: Multiplex PCR assay (Film-array Pneumonia Panel Plus)<br>* The lower tract respiratory samples will be analyzed with Multiplex PCR assay (Film-array Pneumonia Plus).<br>Diagnostic Test: Lower respiratory tract standard culture<br>* 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)<br>Diagnostic Test: Blood sample standard culture<br>* When HAP or VAP are suspected, blood samples from peripheral vein will be collected and analyzed with conventional microbiological methods<br>|
| Active Comparator: Standard culture group (control group)<br>Patients with suspected HAP or VAP in which lower tract respiratory samples are analyzed with standard culture | Procedure: Lower tract respiratory samples<br>* 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<br>Diagnostic Test: Lower respiratory tract standard culture<br>* 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)<br>Diagnostic Test: Blood sample standard culture<br>* When HAP or VAP are suspected, blood samples from peripheral vein will be collected and analyzed with conventional microbiological methods<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients without microbiological diagnosis of HAP/VAP within the first 24 hours | Proportion of patients where a microbiological diagnosis of HAP/VAP is not avaiable within the first 24 hours | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of antibiotic de-escalation as a consequence of microbiological results | Proportion of patients in which antibiotic therapy has been modified from broad-spectrum empirical to targeted, due to microbiological results | 4 days | 
| Time to antibiotic de-escalation and optimal therapy | Period of time from empirical antibiotic therapy initiation to modification due to microbiological results | 4 days | 
| Mechanical Ventilation free-days | Number of days from enrollment in which the patients is not mechanically ventilated | 14 and 28 days | 
| Rate of MDR infection | Proportion of patients who suffered from infection caused by multidrug resistant germ | 28 days | 
| Lenght of intensive care unit stay | Period of time from enrollment in which the patient is admitted to the intensive care unit | 60 days | 
| Lenght of hospital stay | Period of time from enrollment in which the patient is admitted to the hospital | 60 days | 
| In-Intensive care unit mortality | All-cause mortality, assessed during ICU stay | 28 days and 60 days | 
| 28 days and 60 days mortality | All-cause mortality | 28 days and 60 days | 
| SOFA score | Measured SOFA score after 2,3,7 and 14 days from enrollment | 14 days | 
| Diagnostic concordance | Proportion of patients in the interventional group, in which microbiological diagnosis is concordant when assessed with PCR array and standard culture | 4 days | 
| Adverse event | Proportion of patients in which any adverse event is registered | 28 days | 
| In-Hospital mortality | All-cause mortality, assessed during Hospital stay | 28 days and 60 days |