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

VAP - Ventilator Associated Pneumonia Clinical Trial

— LIGHTNING  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05952648
• Other study ID #: 5768
• Status: Recruiting
• Phase: N/A
• Start date: April 3, 2024
• Est. completion date: April 1, 2025

Study information

• Verified date: May 2024
• Source: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Contact: Gennaro De Pascale, MD
• Phone: +393208998173
• Email: gennaro.depascale[@]policlinicogemelli.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 126
• Est. completion date: April 1, 2025
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Healthcare-Associated Pneumonia
• Pneumonia
• Pneumonia, Ventilator-Associated
• VAP - Ventilator Associated Pneumonia

Intervention

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).
• 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)
• Blood sample standard culture
When HAP or VAP are suspected, blood samples from peripheral vein will be collected and analyzed with conventional microbiological methods

Locations

Country	Name	City	State
Italy	S. Orsola Research Hospital	Bologna
Italy	Ospedale Careggi	Firenze
Italy	Modena Policlinico	Modena
Italy	Fondazione Policlinico Universitario "A. GEMELLI" IRCCS	Roma

Sponsors (2)

Lead Sponsor	Collaborator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Catholic University of the Sacred Heart

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Time to antibiotic de-escalation and optimal therapy	Period of time from empirical antibiotic therapy initiation to modification due to microbiological results	4 days
Secondary	Mechanical Ventilation free-days	Number of days from enrollment in which the patients is not mechanically ventilated	14 and 28 days
Secondary	Rate of MDR infection	Proportion of patients who suffered from infection caused by multidrug resistant germ	28 days
Secondary	Lenght of intensive care unit stay	Period of time from enrollment in which the patient is admitted to the intensive care unit	60 days
Secondary	Lenght of hospital stay	Period of time from enrollment in which the patient is admitted to the hospital	60 days
Secondary	In-Intensive care unit mortality	All-cause mortality, assessed during ICU stay	28 days and 60 days
Secondary	28 days and 60 days mortality	All-cause mortality	28 days and 60 days
Secondary	SOFA score	Measured SOFA score after 2,3,7 and 14 days from enrollment	14 days
Secondary	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
Secondary	Adverse event	Proportion of patients in which any adverse event is registered	28 days
Secondary	In-Hospital mortality	All-cause mortality, assessed during Hospital stay	28 days and 60 days