Impact of Rapid Pathogen Detection in ICU Patients With Suspected Pneumonia on Antimicrobial Therapy (IRISPAT-1)

Impact of Rapid Pathogen Detection in ICU Patients With Suspected Pneumonia on Antimicrobial Therapy: a Pilot, Randomized, Controlled Open-label Feasibility Trial (IRISPAT-1)

The goal of this intervention trial is to determine the feasibility, safety, and potential impact of rapid respiratory pathogen detection by FA Pneumonia Panel on antibiotic therapy in mechanically ventilated critically ill patients with suspected pneumonia.

Participants will randomized to either have an urgent BioFire FA Pneumonia Panel assay performed or recieve standard of care to guide antimicrobial therapy and treatment of pneumonia.

Study Overview

• Status: Completed
• Conditions: Pneumonia; Critically Ill
• Intervention / Treatment: Diagnostic test: FA Pneumonia Panel

Detailed Description

Pneumonia is the most common cause of sepsis requiring admission to the intensive care unit (ICU). Molecular pathogen detection techniques such as polymerase chain reaction (PCR) may help optimize antimicrobial therapy. Its utility for diagnosing respiratory viral infections such as influenza is well established, and was an essential diagnostic tool during the coronavirus 2019 (COVID-19) pandemic. However, its use remains limited for bacterial pathogens. The rationale to use PCR based bacterial detection to facilitate antibiotic stewardship is threefold. First, it may shorten the time to pathogen detection. Second, it has improved sensitivity over conventional culture techniques, particularly for pathogens that are difficult to culture. Third, it can detect resistant genes to inform antimicrobial sensitivity. Taken together, utilization of bacterial PCR may shorten time to appropriate antimicrobial therapy and minimize injudicious use of broad-spectrum antimicrobials in patients who do not have infection from MDRO.

The BioFire® FilmArray® Pneumonia Panel (FA Pneumonia Panel) is a PCR based in vitro assay which rapidly identifies 8 viral and 18 bacterial common pathogens in tracheal aspirate and bronchoalveolar lavage (BAL) samples. Clinical studies showed that FA Pneumonia Panel on BAL specimens have sensitivity of 75 to 100% and specificity of >91% for the pathogens tested. Retrospective analysis suggests utilizing FA Pneumonia Panel may facilitate discontinuation or de-escalation of antimicrobials in 48% of patients with an average reduction of 6 antibiotic days. However, currently there are no randomized controlled trials that assessed the efficacy of FA Pneumonia Panel on improving antimicrobial stewardship.

Addition of FA Pneumonia Panel to standard care should shorten time to pathogen and resistance detection, enhance sensitivity over conventional microbiological cultures and shorten time to appropriate antimicrobial therapy by reducing over-narrow and over-broad coverage. Robust clinical trials are now needed to test these hypotheses. We propose to conduct a pilot, randomized, controlled open-label trial designed to determine the feasibility, safety, and potential impact of rapid respiratory pathogen detection by FA Pneumonia Panel on antibiotic therapy in 40 mechanically ventilated critically ill patients with suspected pneumonia.

The goal is to determine the feasibility, safety, and potential impact of rapid respiratory pathogen detection by BioFire FilmArray Pneumonia Panel on antimicrobial therapy in 40 mechanically ventilated critically ill patients with suspected pneumonia.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• adult (≥18 years old) ICU patients
• mechanical ventilation
• new antibiotic prescription within 24 hours for suspected community acquired, healthcare or ventilator associated pneumonia
• suspected pneumonia is defined as any of purulent sputum, cough, fever, shortness of breath, hypoxia, hypercapnia or abnormal white cell count AND chest infiltrates on imaging
• need for antibiotics other than suspected respiratory infection
• aspiration pneumonia
• suspected pneumonia due to tuberculosis
• known respiratory pathogens within 7 days prior to randomization
• given empirical antimicrobials for suspected Stenotrophomonas infection
• lack of sufficient respiratory samples for culture and FA Pneumonia Panel
• not expected to survive beyond 48 hours
• limitation of therapy prior to recruitment
• prisoners
• allergy to antibiotics
• immunosuppression from long term steroid of at least 5 mg/day or chemotherapy or HIV or haematological disease
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FA Pneumonia Panel Guided Group; Patients in the FA Pneumonia Panel guided group will have a BioFire® FilmArray® Pneumonia Panel assay performed as soon as possible but within 24 hours of new antibiotic prescription for suspected respiratory infection in addition to all the investigations performed in standard care. Based on the rapid test results, antimicrobial therapy will be adjusted according to a pre-determined treatment algorithm and antimicrobial guidelines. The treatment algorithm and antimicrobial guidelines were based on the latest hospital antibiogram, procalcitonin protocol, and consensus recommendations from microbiologists, infectious disease experts and intensive care physicians at our hospital. The treating clinical team will also be given the standard microbiological culture with sensitivity results when available. The treating clinical team may override the pre-determined antimicrobial algorithm for any clinical reason at any time and the rationale will be recorded.	Diagnostic test: FA Pneumonia Panel; A single BioFire® FilmArray® Pneumonia Panel assay will be performed on a respiratory clinical specimen.
No Intervention: Standard Care Group; Patients in the standard care group will receive antimicrobial therapy guided by conventional microbiological cultures and standardized procalcitonin protocol. Choice of antimicrobial agent is based on use of the narrowest-spectrum antimicrobial agent possible according to culture sensitivity. Current standard investigations for any patient mechanically ventilated for suspected pneumonia in our ICU includes two sets of blood cultures, alternative day procalcitonin, respiratory specimen of tracheal aspirate or bronchoalveolar lavage for bacterial gram stain and cultures, respiratory viral PCR and urine streptococcus and legionella antigen. FA Pneumonia Panel will be performed from concurrent respiratory samples in the standard care group at the end of the study and the results will not be used by the treating clinical team for treatment decisions. Blinded results will only be available to the antimicrobial review panel for outcome assessment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time interval to appropriate antimicrobial therapy	Defined as the time interval (hours) from time of randomization to earliest time that appropriate antimicrobial therapy is achieved as determined by the antimicrobial stewardship review panel.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with appropriate antimicrobial therapy at 48 hours after randomization	Defined as the proportion of patients with appropriate antimicrobial therapy at 48 hours after randomization as determined by the antimicrobial stewardship review panel	48 hours
Time interval to pathogen detection	Defined as the time interval (hours) between culture or FA Pneumonia Panel sampling time to reporting time that confirmed the presence (with sensitivity pattern) or absence any causative pathogens from the tracheal aspirate or BAL sample taken after randomization.	7 days
Duration of antimicrobial therapy between FA Pneumonia Panel guided and standard care group	Defined as the duration (hours) of antimicrobial therapy given after randomization until hospital discharge	28 days
Proportion of patients on broad-spectrum antibiotics at 48 hours after randomization	Defined as the proportion of patients who are prescribed carbapenem, tigecycline, ceftolozane-tazobactam, ceftaroline, ceftazidime/avibactam, linezolid, vancomycin, daptomycin, aztreonam or cefiderocol at 48 hours after randomization.	48 hours
Ventilator free days	Defined as the number of days free from mechanical ventilation 28 days after randomization.	28 days
Vasopressor free days	Defined as the number of days free from vasopressor therapy 28 days after randomization.	28 days
ICU length of stay	Defined as the duration (days) of ICU length of stay	28 days
28-day mortality	Defined as the all-cause mortality rate on or before 28 days after randomization	28 days
Proportion of patients who require re-initiation or escalation of antimicrobial therapy after 48 hours of discontinuation or de-escalation	Defined as the proportion of patients who required restart or escalation of antimicrobial therapy after discontinuation or de-escalation after ≥ 48 hours	7 days

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2024
• Primary Completion (Actual): November 1, 2025
• Study Completion (Actual): November 1, 2025

Study Registration Dates

• First Submitted: June 23, 2024
• First Submitted That Met QC Criteria: June 23, 2024
• First Posted (Actual): June 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: infection; intensive care; antibiotic stewardship; antimicrobial; antibiotics; multidrug resistant organisms
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pathological Conditions, Signs and Symptoms; Critical Illness; Pneumonia; Infections
• Other Study ID Numbers: 2023.327

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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