Pneumonia Direct Pilot

NCT ID: NCT06181669

Last Updated: 2025-09-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

250 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-04-12

Study Completion Date

2025-12-30

Brief Summary

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The Pneumonia Direct Pilot study is designed to assess whether combining molecular diagnostics for bacteria and AMR markers with host-response profiling improves agreement and predictive value for the diagnosis of VAP versus an adjudicated clinical reference standard. The feasibility design is intended to inform future interventional studies that will investigate the clinical impact of combined pathogen- and host-directed testing approaches.

Detailed Description

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This is a prospective, observational, diagnostic, feasibility study to determine the accuracy of pathogen- and host-directed testing for the diagnosis of VAP. Newly intubated adult patients admitted to the ICU will be assessed for eligibility around the time of intubation according to the inclusion/exclusion criteria. Screening and consent can occur any time within 48 hours of a patient being intubated. Between 48 and 60 hours after intubation, eligible participants will have blood drawn and dedicated research aliquots from SOC ETS samples retrieved. The dedicated research aliquots from SOC ETS samples will be obtained simultaneously with routine sampling for microbiologic testing or, when this is not possible, during routine suctioning as a part of standard airway care. Collection of other clinical data may occur 24 to 72 hours after intubation.

Participants will be followed daily for a clinical change for up to 14 days from the time of intubation. Clinical change is defined as a clinical suspicion of new-onset VAP that prompts the collection of lower respiratory tract secretions for routine microbiologic testing and initiation, continuation, or modification of antibiotic therapy for a pneumonia indication.

Participants who experience a clinical change will have additional blood samples drawn and dedicated aliquots of the sample retrieved from standard-of-care ETS procedures. Additionally, if available, leftover bronchoalveolar lavage (BAL) will be reclaimed, and respiratory and blood bacterial isolates will be obtained from SOC cultures. Participants will be followed through the diagnosis of clinical change and finalization of all local microbiological and radiological results obtained as a part of usual care. Clinical data will be recorded through medical record review.

Participants who do not experience a clinical change will be followed through extubation, ICU discharge, death, or for up to 14 days after intubation - whichever comes first. Participants who do not have a clinical change will not undergo additional sample collection.

Clinical change events will be used to assess whether the participant meets the clinical case definition (FDA criteria) for VAP: VAP-positive (VAP+) or VAP-negative (VAP-) categories will be obtained by an algorithm linked to the eCRF data. The VAP clinical case definition will be adjudicated against the participants' clinical data and microbiological evidence and the certainty of the VAP diagnosis will be classified as follows: Prove, Probable, Possible VAP, or No VAP. Every participant with a clinical change will be assessed for the presence of an extrapulmonary infection. Extrapulmonary infection will be classified as follows: Proven, Possible, or No Infection.

Evaluable participant specimens will be sent to a central laboratory for distribution to the testing centers that will perform the index testing. This study will compare pathogen-directed tests and host biomarker tests. Pathogen-directed tests detect and identify the most common causes of bacterial pneumonia, while host biomarker tests assess the host's immune response to infection. Testing centers will be blinded to whether the samples were collected at baseline or clinical change. Neither the study sites, participants, nor adjudicators will receive the results from the index testing.

Conditions

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Pneumonia, Bacterial Ventilator Associated Pneumonia

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Study Groups

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Standard of Care

There are no interventions in this study. Standard of care activities will be captured in the eCRF and samples will be collected and tested. Results will not be returned to the sites or participants.

Pathogen and Host Directed testing

Intervention Type DIAGNOSTIC_TEST

This study will compare up to 6 pathogen-directed tests and 3 host biomarker tests. Pathogen-directed tests detect and identify the most common causes of bacterial pneumonia, while host biomarker tests assess the host's immune response to infection. Testing will occur at various testing centers.

Evaluable participant specimens will be sent to a central laboratory for distribution to the testing centers that will perform the index testing. Testing centers will be blinded to whether the samples were collected at baseline or clinical change. Further, each testing center will prepare and test the specimens according to documented procedures, then transfer the testing results to the ARLG Statistics and Data Management Center for analysis. Neither the study sites, participants, nor adjudicators will receive the results from the index testing. After the study, untested aliquots of specimens will be stored in the ARLG Physical Biorepository.

Interventions

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Pathogen and Host Directed testing

This study will compare up to 6 pathogen-directed tests and 3 host biomarker tests. Pathogen-directed tests detect and identify the most common causes of bacterial pneumonia, while host biomarker tests assess the host's immune response to infection. Testing will occur at various testing centers.

Evaluable participant specimens will be sent to a central laboratory for distribution to the testing centers that will perform the index testing. Testing centers will be blinded to whether the samples were collected at baseline or clinical change. Further, each testing center will prepare and test the specimens according to documented procedures, then transfer the testing results to the ARLG Statistics and Data Management Center for analysis. Neither the study sites, participants, nor adjudicators will receive the results from the index testing. After the study, untested aliquots of specimens will be stored in the ARLG Physical Biorepository.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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Respiratory Pathogen ID/AMR Enrichment Panel (Illumina) Metagenomic Next Generation Sequencing (Illumina) T2 Bacteria Panel (T2 Biosystems) T2 Resistance Panel (T2 Biosystems) Procalcitonin (Abbott) TriVerity host (Inflammatix) Host gene expression FilmArray Pneumonia Panel (BioFire)

Eligibility Criteria

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Inclusion Criteria

1. Are ≥18 years old
2. Are newly intubated for less than 48 hours and for reasons other than suspected bacterial pneumonia or suspected acute bacterial infection
3. Are expected to require intubation for at least 48 hours, per the discretion of the treating clinician
4. Are able to provide protocol-accepted consent (legally authorized representative \[LAR\] is acceptable)
5. Are expected to live long enough to receive a VAP diagnosis, at the discretion of the treating clinician
6. Are able to provide study-required biological samples

Exclusion Criteria

1. Have a witnessed or suspected aspiration event prompting the need for current, new intubation
2. Have known active lung cancer or metastatic disease to a lung
3. Received a lung transplant
4. Have cystic fibrosis
5. Are receiving comfort care
6. Are receiving antibiotic treatment for suspected or proven active acute bacterial infection (eg, pneumonia, tracheobronchitis, sepsis)
7. Have a current or within-the-last-30-days diagnosis of active bacterial pneumonia
8. Were previously enrolled in this trial
9. Require long-term ventilator support
10. Have a tracheostomy tube in place
11. Are currently participating in an interventional drug or device study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kimberly E Hanson, MD, MHS

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

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Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Corewell (William Beaumont)

Royal Oak, Michigan, United States

Site Status

Washington University School of Medicine in St. Louis

St Louis, Missouri, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

References

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Papazian L, Klompas M, Luyt CE. Ventilator-associated pneumonia in adults: a narrative review. Intensive Care Med. 2020 May;46(5):888-906. doi: 10.1007/s00134-020-05980-0. Epub 2020 Mar 10.

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Safdar N, Dezfulian C, Collard HR, Saint S. Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med. 2005 Oct;33(10):2184-93. doi: 10.1097/01.ccm.0000181731.53912.d9.

Reference Type BACKGROUND
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Kuti EL, Patel AA, Coleman CI. Impact of inappropriate antibiotic therapy on mortality in patients with ventilator-associated pneumonia and blood stream infection: a meta-analysis. J Crit Care. 2008 Mar;23(1):91-100. doi: 10.1016/j.jcrc.2007.08.007.

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Nussenblatt V, Avdic E, Berenholtz S, Daugherty E, Hadhazy E, Lipsett PA, Maragakis LL, Perl TM, Speck K, Swoboda SM, Ziai W, Cosgrove SE. Ventilator-associated pneumonia: overdiagnosis and treatment are common in medical and surgical intensive care units. Infect Control Hosp Epidemiol. 2014 Mar;35(3):278-84. doi: 10.1086/675279. Epub 2014 Feb 3.

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Klompas M. Does this patient have ventilator-associated pneumonia? JAMA. 2007 Apr 11;297(14):1583-93. doi: 10.1001/jama.297.14.1583.

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Gaston DC, Miller HB, Fissel JA, Jacobs E, Gough E, Wu J, Klein EY, Carroll KC, Simner PJ. Evaluation of Metagenomic and Targeted Next-Generation Sequencing Workflows for Detection of Respiratory Pathogens from Bronchoalveolar Lavage Fluid Specimens. J Clin Microbiol. 2022 Jul 20;60(7):e0052622. doi: 10.1128/jcm.00526-22. Epub 2022 Jun 13.

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Sotillo-Diaz JC, Bermejo-Lopez E, Garcia-Olivares P, Peral-Gutierrez JA, Sancho-Gonzalez M, Guerrero-Sanz JE. [Role of plasma procalcitonin in the diagnosis of ventilator-associated pneumonia: systematic review and metaanalysis]. Med Intensiva. 2014 Aug-Sep;38(6):337-46. doi: 10.1016/j.medin.2013.07.001. Epub 2013 Sep 12. Spanish.

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Langelier C, Kalantar KL, Moazed F, Wilson MR, Crawford ED, Deiss T, Belzer A, Bolourchi S, Caldera S, Fung M, Jauregui A, Malcolm K, Lyden A, Khan L, Vessel K, Quan J, Zinter M, Chiu CY, Chow ED, Wilson J, Miller S, Matthay MA, Pollard KS, Christenson S, Calfee CS, DeRisi JL. Integrating host response and unbiased microbe detection for lower respiratory tract infection diagnosis in critically ill adults. Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):E12353-E12362. doi: 10.1073/pnas.1809700115. Epub 2018 Nov 27.

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Bergin SP, Coles A, Calvert SB, Farley J, Powers JH, Zervos MJ, Sims M, Kollef MH, Durkin MJ, Kabchi BA, Donnelly HK, Bardossy AC, Greenshields C, Rubin D, Sun JL, Chiswell K, Santiago J, Gu P, Tenaerts P, Fowler VG Jr, Holland TL. PROPHETIC: Prospective Identification of Pneumonia in Hospitalized Patients in the ICU. Chest. 2020 Dec;158(6):2370-2380. doi: 10.1016/j.chest.2020.06.034. Epub 2020 Jun 29.

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Bergin SP, Calvert SB, Farley J, Sun JL, Chiswell K, Dieperink W, Kluytmans J, Lopez-Delgado JC, Leon-Lopez R, Zervos MJ, Kollef MH, Sims M, Kabchi BA, Rubin D, Santiago J, Natarajan M, Tenaerts P, Fowler VG, Holland TL, Bonten MJ, Hullegie SJ. PROPHETIC EU: Prospective Identification of Pneumonia in Hospitalized Patients in the Intensive Care Unit in European and United States Cohorts. Open Forum Infect Dis. 2022 May 9;9(7):ofac231. doi: 10.1093/ofid/ofac231. eCollection 2022 Jul.

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Related Links

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https://www.biofiredx.com/products/the-filmarray-panels/filmarray-pneumonia

The BioFire® FilmArray®Pneumonia (PN) Panel. BioFire Diagnostics. 2023.

https://www.fda.gov/media/79516/download

FDA. Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia: Developing Drugs for Treatment Guidance for Industry. Accessed October 20, 2022.

Other Identifiers

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5UM1AI104681

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00113767

Identifier Type: -

Identifier Source: org_study_id

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