Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06605352
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-18
Brief Title:
Clinical Impact of Rapid Molecular Testing for Pathogens in Patients With Severe Acute Respiratory Illness A Pragmatic Trial
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Clinical Impact of Rapid Molecular Testing for Pathogens in Patients With Severe Acute Respiratory Illness A Pragmatic Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CIRT-RMT-SARI
Brief Summary:
Community-acquired pneumonia CAP is among the most common reasons for emergency department ED visits A clear understanding of the likely pathogens is essential for the rapid institution of adequate antimicrobial therapy Due to the indistinguishable clinical symptoms between viral and bacterial pathogens patients with viral respiratory infection are usually under-evaluated while unnecessary antibacterial agents are more likely to be administered With the development of highly sensitive end-to-end point-of-care POC multiplex PCR system rapid diagnosis of respiratory pathogens for CAP in the ED becomes possible Our previous NTUH-VGH cooperative research project demonstrated POC respiratory viral testing in conjunction with procalcitonin test can reduce the length of hospital stay and antibiotic consumption However viral testing alone cannot guide precision antimicrobial treatment A complete pneumonia pathogen testing panel should include bacteria virus atypical pathogens and resistant genes In addition such test need to be completed within about time at a reasonable cost The difficult missing has been recently achieved The BIOFIREFILMARRAY Pneumonia Panel is the only FDA approved mPCR test that can test 18 bacteria 11 Gram negative 4 Gram positive and 3 atypical 7 antibiotic resistance markers and 9 viruses in one test within 45 minutes Currently the world is eagerly to learn how this new diagnostic technology can transform the clinical management of pneumonia With this in mind the aim of this study is to evaluate the impact of POC pneumonia pathognome wide testing on the antimicrobial use and outcome of patients We will perform an open label pragmatic parallel comparison between patients withwithout the test The results will inform the pneumonia guideline Subsequent health economic analysis based on this study will be important to the reimbursement policy of the health insurance of Taiwan
Detailed Description:
Community-acquired pneumonia is among the most common reasons for emergency department ED visits and can be caused by both viral and bacterial pathogens A clear understanding of the likely pathogens is essential for the rapid institution of adequate antiviral or antibiotic therapy Due to the indistinguishable clinical symptoms between viral and bacterial pathogens patients with viral respiratory infection are usually undervalued while unnecessary antibacterial agents are more likely to be administered The principal bacterial causes of CAP are well described with Streptococcus pneumoniae being the most important pathogen in all age groups Recent studies and our previous work showed viral associated CAP can be responsible for 20 to 30 of CAP Therefore laboratory tests providing accurate and timely determination of the infectious agents associated with CAP are important A broad array of tests is available to detect viral respiratory agents Rapid antigen tests are available for influenza A and B and respiratory syncytial virus RSV but these tests have low sensitivity and specificity
Molecular diagnostic tests using the polymerase chain reaction PCR method to detect RNA or DNA of the infectious agents have improved the ability to detect both viral and bacterial pathogens in clinical samples but are technically challenging and time consuming The advent of sensitive point-of-care POC molecular detection methods has made rapid diagnosis of respiratory virus infections possible A POC systems that automates the real-time PCR process and integrates sample preparation amplification detection and analysis into one complete process has been developed and approved by the FDA Initial studies demonstrated that such POC multiplex PCR systems identified previously under-evaluated viral or atypical infections in ED dyspneic patients Despite the availability of highly accurate viral testing results discontinuation of de-escalation of antibiotics still raises concerns because polymicrobial infections involving bacterial and viral pathogens is common in the older adults An ideal pathogen diagnostic tool for CAP that can guide precise prescription of antibiotics should therefore include the following three features first including a wide array of both common viral and bacterial pathogens for CAP second including common drug resistance genes for bacterial pathogens and lastly easy operation with quick turnaround time and high accuracy
Such diagnostic tool has recently been developed The BIOFIRE FILMARRAY Pneumonia Panel plus tests for 18 bacteria 11 Gram negative 4 Gram positive and 3 atypical 7 antibiotic resistance markers and 9 viruses that cause pneumonia and other lower respiratory tract infections The target bacteria included Acinetobacter calcoaceticus-baumannii complex Enterobacter cloacae Escherichia coli Haemophilus influenzae Klebsiella aerogenes Klebsiella oxytoca Klebsiella pneumoniae group Moraxella catarrhalis Proteus spp Pseudomonas aeruginosa Serratia marcescens Staphylococcus aureus Streptococcus agalactiae Streptococcus pneumoniae Streptococcus pyogenes Seven antibiotics genes include ESBL CTX-M Carbapenemases KPC NDM Oxa48-like VIM IMP Methicillin Resistance mecAmecC and MREJ The atypical pathogens include Legionella pneumophila Mycoplasma pneumoniae and Chlamydia pneumoniae The virus included Influenza A Influenza B Adenovirus Coronavirus Parainfluenza virus Respiratory Syncytial virus Human RhinovirusEnterovirus Human Metapneumovirus and even Middle East Respiratory Syndrome Coronavirus MERS-CoV The Filmarray system is a US FDA system that integrates sample preparation nucleic acid extraction and purification amplification detection and analysis into one simple system that requires just 2 minutes of hands-on time with a total run time of about one hour Currently the overall sensitivity and specificity for bronchoalveolar BAL-like samples of 962 and 983 respectively and for sputum samples a sensitivity and specificity of 963 and 972 respectively
In this study we aim to assess the impact of implementation of POC molecular testing for pneumonia pathogens in conjunction with procalcitonin tests on elderly patients presenting to the ED with severe acute respiratory illness We will conduct a prospective cohort study in the EDs of two urban medical centers Clinical impact will be evaluated through the comparison between the experimental cohort with a randomly selected control cohort in a parallel fashion In addition to POC molecular test we will also test procalcitonin on these patients With a highly sensitive POC molecular test it is likely the detection of colonized pathogens will greatly increase PCT is a precursor of calcitonin that is constitutively secreted by C cells of the thyroid gland and K cells of the lung In healthy individuals PCT is normally undetectable below 001 ngmL When stimulated by endotoxin PCT is rapidly produced by parenchymal tissue throughout the body Unlike C-reactive protein PCT does not respond to sterile inflammation or viral infection Multiple randomized controlled trials have demonstrated that procalcitonin levels of under 025 µgL can guide the decision to withhold antibiotics or stop therapy early In addition a procalcitonin levels of under 01 µgL can indicate colonization We hypothesize the new diagnostic approach would better guide the antibiotic treatment and ultimately improve patients outcome
Molecular diagnostic tests using the polymerase chain reaction PCR method to detect RNA or DNA of the infectious agents have improved the ability to detect both viral and bacterial pathogens in clinical samples but are technically challenging and time consuming The advent of sensitive point-of-care POC molecular detection methods has made rapid diagnosis of respiratory virus infections possible A POC systems that automates the real-time PCR process and integrates sample preparation amplification detection and analysis into one complete process has been developed and approved by the FDA Initial studies demonstrated that such POC multiplex PCR systems identified previously under-evaluated viral or atypical infections in ED dyspneic patients Despite the availability of highly accurate viral testing results discontinuation of de-escalation of antibiotics still raises concerns because polymicrobial infections involving bacterial and viral pathogens is common in the older adults An ideal pathogen diagnostic tool for CAP that can guide precise prescription of antibiotics should therefore include the following three features first including a wide array of both common viral and bacterial pathogens for CAP second including common drug resistance genes for bacterial pathogens and lastly easy operation with quick turnaround time and high accuracy
Such diagnostic tool has recently been developed The BIOFIRE FILMARRAY Pneumonia Panel plus tests for 18 bacteria 11 Gram negative 4 Gram positive and 3 atypical 7 antibiotic resistance markers and 9 viruses that cause pneumonia and other lower respiratory tract infections The target bacteria included Acinetobacter calcoaceticus-baumannii complex Enterobacter cloacae Escherichia coli Haemophilus influenzae Klebsiella aerogenes Klebsiella oxytoca Klebsiella pneumoniae group Moraxella catarrhalis Proteus spp Pseudomonas aeruginosa Serratia marcescens Staphylococcus aureus Streptococcus agalactiae Streptococcus pneumoniae Streptococcus pyogenes Seven antibiotics genes include ESBL CTX-M Carbapenemases KPC NDM Oxa48-like VIM IMP Methicillin Resistance mecAmecC and MREJ The atypical pathogens include Legionella pneumophila Mycoplasma pneumoniae and Chlamydia pneumoniae The virus included Influenza A Influenza B Adenovirus Coronavirus Parainfluenza virus Respiratory Syncytial virus Human RhinovirusEnterovirus Human Metapneumovirus and even Middle East Respiratory Syndrome Coronavirus MERS-CoV The Filmarray system is a US FDA system that integrates sample preparation nucleic acid extraction and purification amplification detection and analysis into one simple system that requires just 2 minutes of hands-on time with a total run time of about one hour Currently the overall sensitivity and specificity for bronchoalveolar BAL-like samples of 962 and 983 respectively and for sputum samples a sensitivity and specificity of 963 and 972 respectively
In this study we aim to assess the impact of implementation of POC molecular testing for pneumonia pathogens in conjunction with procalcitonin tests on elderly patients presenting to the ED with severe acute respiratory illness We will conduct a prospective cohort study in the EDs of two urban medical centers Clinical impact will be evaluated through the comparison between the experimental cohort with a randomly selected control cohort in a parallel fashion In addition to POC molecular test we will also test procalcitonin on these patients With a highly sensitive POC molecular test it is likely the detection of colonized pathogens will greatly increase PCT is a precursor of calcitonin that is constitutively secreted by C cells of the thyroid gland and K cells of the lung In healthy individuals PCT is normally undetectable below 001 ngmL When stimulated by endotoxin PCT is rapidly produced by parenchymal tissue throughout the body Unlike C-reactive protein PCT does not respond to sterile inflammation or viral infection Multiple randomized controlled trials have demonstrated that procalcitonin levels of under 025 µgL can guide the decision to withhold antibiotics or stop therapy early In addition a procalcitonin levels of under 01 µgL can indicate colonization We hypothesize the new diagnostic approach would better guide the antibiotic treatment and ultimately improve patients outcome
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None