MASTERMIND-Pneumonia Study (Also Known as Pneumonia Direct Pilot)

NCT06181669 | Completed

• 2 other identifiers: Pro001137675UM1AI104681
• Study Type: observational
• Target: 173
• Locations: 1 country
• Sites: 4

Brief Summary

The MASTERMIND-Pneumonia Study (also known as 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.

Conditions

Pneumonia, Bacterial; Ventilator Associated Pneumonia

Outcome Measures

Primary Outcomes (9)

• The number of participants with positive results on the Respiratory Pathogen ID/AMR Enrichment Panel (Illumina)

  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)

  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)

  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)

  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)

  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)

  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

  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)

  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

  * 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 Outcomes (1)

• 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

  through extubation, ICU discharge, death, or for up to 14 days after intubation - whichever comes first

Study Arms (1)

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

Interventions

Pathogen and Host Directed testing 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.

Also known as: 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)

Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Duke University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (4)

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Corewell (William Beaumont)

Royal Oak, Michigan, 48073, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (16)

• 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.

  PMID: 32157357 BACKGROUND

• 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.

  PMID: 16215368 BACKGROUND

• 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.

  PMID: 18359426 BACKGROUND

• 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.

  PMID: 24521594 BACKGROUND

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

  PMID: 17426278 BACKGROUND

• Khan S, Liu J, Xue M. Transmission of SARS-CoV-2, Required Developments in Research and Associated Public Health Concerns. Front Med (Lausanne). 2020 Jun 9;7:310. doi: 10.3389/fmed.2020.00310. eCollection 2020.

  PMID: 32582747 BACKGROUND

• Murphy CN, Fowler R, Balada-Llasat JM, Carroll A, Stone H, Akerele O, Buchan B, Windham S, Hopp A, Ronen S, Relich RF, Buckner R, Warren DA, Humphries R, Campeau S, Huse H, Chandrasekaran S, Leber A, Everhart K, Harrington A, Kwong C, Bonwit A, Dien Bard J, Naccache S, Zimmerman C, Jones B, Rindlisbacher C, Buccambuso M, Clark A, Rogatcheva M, Graue C, Bourzac KM. Multicenter Evaluation of the BioFire FilmArray Pneumonia/Pneumonia Plus Panel for Detection and Quantification of Agents of Lower Respiratory Tract Infection. J Clin Microbiol. 2020 Jun 24;58(7):e00128-20. doi: 10.1128/JCM.00128-20. Print 2020 Jun 24.

  PMID: 32350043 BACKGROUND

• Charalampous T, Alcolea-Medina A, Snell LB, Williams TGS, Batra R, Alder C, Telatin A, Camporota L, Meadows CIS, Wyncoll D, Barrett NA, Hemsley CJ, Bryan L, Newsholme W, Boyd SE, Green A, Mahadeva U, Patel A, Cliff PR, Page AJ, O'Grady J, Edgeworth JD. Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units. Genome Med. 2021 Nov 17;13(1):182. doi: 10.1186/s13073-021-00991-y.

  PMID: 34784976 BACKGROUND

• 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.

  PMID: 35695488 BACKGROUND

• 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.

  PMID: 24035696 BACKGROUND

• Kostaki A, Wacker JW, Safarika A, Solomonidi N, Katsaros K, Giannikopoulos G, Koutelidakis IM, Hogan CA, Uhle F, Liesenfeld O, Sweeney TE, Giamarellos-Bourboulis EJ. A 29-MRNA HOST RESPONSE WHOLE-BLOOD SIGNATURE IMPROVES PREDICTION OF 28-DAY MORTALITY AND 7-DAY INTENSIVE CARE UNIT CARE IN ADULTS PRESENTING TO THE EMERGENCY DEPARTMENT WITH SUSPECTED ACUTE INFECTION AND/OR SEPSIS. Shock. 2022 Sep 1;58(3):224-230. doi: 10.1097/SHK.0000000000001970. Epub 2022 Aug 26.

  PMID: 36125356 BACKGROUND

• 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.

  PMID: 30482864 BACKGROUND

• Kalantar KL, Neyton L, Abdelghany M, Mick E, Jauregui A, Caldera S, Serpa PH, Ghale R, Albright J, Sarma A, Tsitsiklis A, Leligdowicz A, Christenson SA, Liu K, Kangelaris KN, Hendrickson C, Sinha P, Gomez A, Neff N, Pisco A, Doernberg SB, Derisi JL, Matthay MA, Calfee CS, Langelier CR. Integrated host-microbe plasma metagenomics for sepsis diagnosis in a prospective cohort of critically ill adults. Nat Microbiol. 2022 Nov;7(11):1805-1816. doi: 10.1038/s41564-022-01237-2. Epub 2022 Oct 20.

  PMID: 36266337 BACKGROUND

• 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.

  PMID: 32615191 BACKGROUND

• 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.

  PMID: 35836748 BACKGROUND

• Corneli A, Calvert SB, Powers JH 3rd, Swezey T, Collyar D, Perry B, Farley JJ, Santiago J, Donnelly HK, De Anda C, Blanchard K, Fowler VG Jr, Holland TL. Consensus on Language for Advance Informed Consent in Health Care-Associated Pneumonia Clinical Trials Using a Delphi Process. JAMA Netw Open. 2020 May 1;3(5):e205435. doi: 10.1001/jamanetworkopen.2020.5435.

  PMID: 32442291 BACKGROUND

Related Links

• The BioFire® FilmArray®Pneumonia (PN) Panel. BioFire Diagnostics. 2023.
• FDA. Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia: Developing Drugs for Treatment Guidance for Industry. Accessed October 20, 2022.

Biospecimen

Retention: SAMPLES WITH DNA

Endotracheal suctioning (ETS) fluid samples, Bronchoalveolar (BAL) lavage fluid, bacterial isolates, whole blood, serum, and plasma will be sent to a central research laboratory for host- and pathogen-diagnostic testing. Back up samples will stored at the ARLG Laboratory Center.

MeSH Terms

Conditions

Pneumonia, Bacterial; Pneumonia, Ventilator-Associated

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Healthcare-Associated Pneumonia; Cross Infection; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Kimberly E Hanson, MD, MHS

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2023
• First Posted: December 26, 2023
• Study Start: April 12, 2024
• Primary Completion: July 3, 2025
• Study Completion: July 3, 2025
• Last Updated: April 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Once the primary manuscript has been published
• Access Criteria: Application to the ARLG for use

Locations

US (4)