FilmArray Pneumonia Panel for Antimicrobial Treatment of HAP/VAP in Intensive Care Units

Study Overview
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Brief Summary
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Microbiologic diagnosis of pneumonia is often limited by a long turnaround time of cultures. This randomized trial aims to evaluate the impact of BioFire FilmArray Pneumonia panel on (1) the proportion of appropriate/optimal early antibiotic regimen and (2) the time to the administration of appropriate antibiotics in patients treated for hospital-acquired or ventilator-associated pneumonia (HAP/VAP) in ICU.

Detailed Description
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The study subjects are adults treated for HAP/VAP in ICU, who should be enrolled within 24 hrs since the first administration of antibiotics. Informed consent are obtained from the subjects or their legal proxies. Due to the unique characteristics of ICU and the current COVID-19 pandemic, consent may be obtained via telephone when given by legal proxies; written consent should be obtained later. The subjects who meet the inclusion criteria are randomized into either intervention and control arms in 1:1 ratio. Respiratory specimens from the subjects in the intervention arm are tested with the FilmArray Pneumonia panel. Other routine microbiologic tests are performed for the subjects in both arms. The results are reported via electronic medical record, and the treating physicians may adjust antibiotic regimen with the assistance from the guidance formulated by the study investigators. No intervention is made on the antimicrobial treatment in the control arm. Primary outcomes are (1) the proportion of appropriate/optimal early antibiotic regimen and (2) the time to the administration of appropriate antibiotics.

Official Title
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Single Center, Randomized, Open Label, Prospective Clinical Trial of BioFire FilmArray Pneumonia Panel for Antimicrobial Treatment of Hospital-acquired or Ventilator-associated Pneumonia in Intensive Care Units

Conditions
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Pneumonia, Ventilator-Associated, Pneumonia, Hospital Acquired, Critically Ill

Intervention / Treatment
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* Diagnostic Test: FilmArray Pneumonia panel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 19 years or older Diagnosed with hospital-acquired or ventilator-associated pneumonia and being treated in an intensive care unit Patient or his/her legal proxy agrees to participate and is able to provide informed consent Exclusion Criteria: Has been treated with antibiotic for HAP/VAP for 24 hr or longer Requires antibiotic treatment for indications other than HAP/VAP Bacteria has been isolated from respiratory specimens within 7 days prior to screening Immunocompromised host whose major differential diagnosis includes Pneumocystis jirovecii or cytomegalovirus pneumonia Expected to die within 2 days since screening due to underlying disease Has an advance directive against mechanical ventilation or cardiopulmonary resuscitation Does not want to participate or unable to provide consent Determined to be unfit by the study investigator

Ages Eligible for Study
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Minimum Age: 19 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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention<br>Respiratory specimens from the subjects are tested by the FilmArray Pneumonia panel and the results are reported via an electronic health record system. Treating physicians may adjust empirical antibiotic regimens with assistance from the guidelines formulated by the study investigators. Other microbiologic tests, including cultures, are performed as per routine practice. | Diagnostic Test: FilmArray Pneumonia panel<br>* A rapid molecular diagnostic test designed to detect 27 bacterial and viral species and 6 major resistance genes from respiratory specimens.<br>|
| No Intervention: Control<br>Microbiologic tests, including cultures, are performed as per routine practice. No intervention is made on the antimicrobial treatment in the control arm. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of appropriate/optimal early antibiotic regimen | Appropriate antibiotics: agents active in vitro Optimal antibiotics: appropriate AND not overly broad. Spectrums of antibiotics are categorized with the following hierarchy: colistin > carbapenem > piperacillin-tazobactam/4th generation cephalosporins > other beta-lactams/fluoroquinolones; for gram-positives, glycopeptides/linezolid > no glycopeptides/linezolid) Early antibiotic regimen is defined as antibiotics administered ≤24 hr since the initiation of antibiotic treatment | within 24 hours | 
| The time to the administration of appropriate antibiotics | time interval between the first dose of antibiotics and the first dose of antibiotics confirmed active in vitro | within 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day mortality (all-cause) | death of any cause within 30 days since the initiation of antibiotic treatment | within 30 days | 
| ICU mortality | death of any cause while staying in the ICU within 30 days since the initiation of antibiotic treatment | within 30 days | 
| Hospital and ICU length of stay | length of hospital and ICU stay | Through study completion, an average of 9 months | 
| Ventilator-free day | the number of days that the patient was not on mechanical ventilation within 30 days since the initiation of antibiotic treatment | within 30 days | 
| Dialysis-free day | the number of days that the patient was not on hemodialysis (including continuous renal replacement therapy) within 30 days since the initiation of antibiotic treatment | within 30 days | 
| Incidence of acute kidney injury | Acute kidney injury is defined using the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. | within 30 days | 
| Incidence of Clostridioides difficile infection | C. difficile infection is defined as 3 or more defecations of unformed stool per day with a positive enzyme immunoassay or PCR for C. difficile toxin. | within 30 days | 
| Acquisition of multi-drug resistance organism during hospital stay | Multi-drug resistance (MDR) is defined as an in vitro resistance against 1 or more agents in 3 or more antibiotic classes. Methicillin (or oxacillin) resistance of Staphylococcus and vancomycin resistance of Enterococcus spp. are classified as MDR. | within 30 days | 
| Duration of antibiotic treatment | the number of days that the patient was administered with antibiotics for the treatment of pneumonia within 30 days since the initiation of antibiotic treatment | within 30 days | 
| Total medical cost in the ICU | total medical cost for the patient care in the ICU | within 30 days | 
| Compliance to FilmArray guidance (intervention arm only) | The proportion of early antibiotic regimens that complied with the recommendation in the guidance. | within 30 days |