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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: VAP - Ventilator Associated Pneumonia; HAP - Hospital Acquired Pneumonia
• Intervention / Treatment: 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

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 Type: Interventional
• Enrollment (Estimated): 126
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gennaro De Pascale, MD; Phone Number: +393208998173; Email: gennaro.depascale@policlinicogemelli.it

Study Locations

• Italy
  • Bologna, Italy
    • S. Orsola Research Hospital
    • Contact: Tommaso Tonetti, MD; Email: tommaso.tonetti@unibo.it
  • Firenze, Italy
    • Ospedale Careggi
    • Contact: Bruno Viaggi, MD; Email: bruno.viaggi@gmail.com
  • Modena, Italy
    • Modena Policlinico
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario "A. Gemelli" IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Collaborators: 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 record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: July 5, 2023
• First Submitted That Met QC Criteria: July 17, 2023
• First Posted (Actual): July 19, 2023

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Pneumonia, Ventilator-Associated
• Other Study ID Numbers: 5768

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No