Pneumonia Direct Pilot (PDP)

April 24, 2024 updated by: Duke University
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

250

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Hospital
        • Contact:
        • Principal Investigator:
          • Geehan Suleyman, MD
      • Royal Oak, Michigan, United States, 48073
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine in St. Louis
        • Contact:
        • Principal Investigator:
          • Patrick Mazi, MD
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • University of Pittsburgh Medical Center
        • Contact:
        • Principal Investigator:
          • Ryan Shields, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Intubated adult patients (≥18 years of age) admitted to the ICU will be assessed for eligibility around the time of intubation according to the inclusion/exclusion criteria. Screening and consent may occur at any time within 48 hours of patients being intubated. The target sample size is 250 participants in order to observe approximately 30 clinical VAP-positive cases. Vulnerable patients, including women and minorities, will be included in this study.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
Diagnostic test: 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.

Other Names:
  • 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of participants with positive results on the Respiratory Pathogen ID/AMR Enrichment Panel (Illumina)
Time Frame: Through study completion, or up to 18 months, whichever comes first
This study will compare the results (positive, negative, or no result) of each index test.
Through study completion, or up to 18 months, whichever comes first
The number of participants with positive results on the Metagenomic Next Generation Sequencing (Illumina)
Time Frame: Through study completion, or up to 18 months, whichever comes first
This study will compare the results (positive, negative, or no result) of each index test.
Through study completion, or up to 18 months, whichever comes first
The number of participants with positive results on the T2 Bacteria Panel (T2 Biosystems)
Time Frame: Through study completion, or up to 18 months, whichever comes first
This study will compare the results (positive, negative, or no result) of each index test.
Through study completion, or up to 18 months, whichever comes first
The number of participants with positive results on the T2 Resistance Panel (T2 Biosystems)
Time Frame: Through study completion, or up to 18 months, whichever comes first
This study will compare the results (positive, negative, or no result) of each index test.
Through study completion, or up to 18 months, whichever comes first
The number of participants with positive results on the Procalcitonin (Abbott)
Time Frame: Through study completion, or up to 18 months, whichever comes first
This study will compare the results (positive, negative, or no result) of each index test.
Through study completion, or up to 18 months, whichever comes first
The number of participants with positive results on the TriVerity host (Inflammatix)
Time Frame: Through study completion, or up to 18 months, whichever comes first
This study will compare the results (positive, negative, or no result) of each index test.
Through study completion, or up to 18 months, whichever comes first
The number of participants with positive results on the Host gene expression
Time Frame: Through study completion, or up to 18 months, whichever comes first
This study will compare the results (positive, negative, or no result) of each index test.
Through study completion, or up to 18 months, whichever comes first
The number of participants with positive results on the FilmArray Pneumonia Panel (BioFire)
Time Frame: Through study completion, or up to 18 months, whichever comes first
This study will compare the results (positive, negative, or no result) of each index test.
Through study completion, or up to 18 months, whichever comes first
Number of participants with a clinical diagnosis of VAP at the time of clinical change
Time Frame: day 15

  • Clinical diagnosis of VAP is defined as new findings in each category of signs and imaging

    o At least one of the following signs of inflammation: Fever >=38 °C or =35 °C Leukocytosis (white blood cell count ≥12K/mm3 or ≤4K/mm3) >15% immature neutrophils (bands) AND

    • signs of respiratory worsening. AND
    • New or progressive changes suggestive of bacterial pneumonia from imaging: infiltrate, consolidation, and/or cavitation
  • Clinical change is defined as a clinical suspicion of new onset VAP that prompts collection of lower respiratory tract secretions for routine microbiologic testing and initiation or continuation of empiric antibiotic therapy for a pneumonia indication.
day 15

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with an adjudicated diagnosis of of proven, probable, possible, or no VAP at the time of clinical change utilizing clinical and microbiological information
Time Frame: through extubation, ICU discharge, death, or for up to 14 days after intubation - whichever comes first
- clinical information collected from participants with a clinical change will be reviewed to discern the presence of signs and symptoms of VAP as well as evidence of extrapulmonary infection. Cases of suspected VAP and extra-pulmonary infection will then be classified as proven, probable/possible or no infection using expert adjudication and standardized definitions.
through extubation, ICU discharge, death, or for up to 14 days after intubation - whichever comes first

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Principal Investigator: Kimberly E Hanson, MD, MHS, University of Utah

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 12, 2024

Primary Completion (Estimated)

September 30, 2024

Study Completion (Estimated)

April 1, 2025

Study Registration Dates

First Submitted

November 20, 2023

First Submitted That Met QC Criteria

December 22, 2023

First Posted (Actual)

December 26, 2023

Study Record Updates

Last Update Posted (Actual)

April 25, 2024

Last Update Submitted That Met QC Criteria

April 24, 2024

Last Verified

December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00113767
  • 5UM1AI104681 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

During the analysis process, diagnostic companies will support the testing of some specimens and will provide the resulting data back to the Duke Clinical Research Institute.

Once clinical and laboratory data have been analyzed and the primary manuscript has been published, investigators may apply to the Antibacterial Resistance Leadership Group (ARLG) for use of data. Continued regulatory oversight, Data Use Agreements, and Material Transfer agreements may apply.

IPD Sharing Time Frame

Once the primary manuscript has been published

IPD Sharing Access Criteria

Application to the ARLG for use

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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