TriVerity in the Diagnosis and Prognosis of Emergency Department Patients With Suspected Infections and Suspected Sepsis (SEPSIS-SHIELD)

This study will analyze gene expression and other laboratory data from biological samples collected from participants with suspected respiratory, urinary, intra-abdominal, and/or skin & soft tissue infections; or suspected sepsis of any cause.

Study Overview

• Status: Completed
• Conditions: Respiratory Tract Infections; Sepsis; Urinary Tract Infections; Intra-Abdominal Infections; Skin and Soft Tissue Infection; Suspected Meningitis/Encephalitis or Any Other Infection
• Intervention / Treatment: Diagnostic test: TriVerity

• Study Type: Observational
• Enrollment (Actual): 1441

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece
    • Attikon University Hospital
• United States
  • Alabama
    • Mobile, Alabama, United States, 36617
      • University of South Alabama
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Health Research Institute
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida (UF) - Jacksonville
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Maryland
    • Baltimore, Maryland, United States, 21209
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Essentia Institute of Rural Health
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New Jersey
    • Montclair, New Jersey, United States, 07042
      • Hackensack Meridian Health
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Health
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Health
    • Pittsburgh, Pennsylvania, United States, 15260
      • University of Pittsburgh
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • El Paso, Texas, United States, 79905
      • Texas Tech University Health Sciences Center - El Paso
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients presenting to the emergency departments of enrolling sites with:

1. Suspected infection and one or more abnormal vital signs, OR
2. Patients with suspected sepsis of any cause as defined by a blood culture order by the treating physician and two or more abnormal vital signs

Description

Inclusion Criteria:

1. Age >18 year

2. Suspected acute infection (respiratory, urinary, abdominal, skin & soft-tissue), and at least one of the symptoms OR, Suspected sepsis of any cause as defined by a blood culture order by the treating physician, and at least two of the symptoms:

   • Heart rate: >90 beats/ minute
   • Temperature: >38 C or <36C
   • Respiratory Rate: >20 breaths / minutes or PaO2 of <60 mmHg or SpO2 <90%
   • Systolic blood pressure: <100 mmHg
   • Altered mental status: Per clinical exam
3. Able to provide informed consent, or consent by legally authorized representative.

Exclusion Criteria:

Participants will be ineligible for this study if they meet any of the following criteria:

1. Patient-reported treatment with systemic antibiotics, systemic antiviral agents or systemic antifungal agents within the past 7 days prior to the emergency department study visit. Participants will not be excluded for use of:

   1. Antiviral treatment for HIV infection and hepatitis B and hepatitis C
   2. Topical antibiotics, topical antiviral or topical antifungal agents
   3. Anti-herpes prophylaxis aiding suppression of a recuring herpes infection
   4. Peri-operative (prophylactic) antibiotics
   5. A single dose of antimicrobials during the present ED visit (<10h before blood draw); note single dose can be considered mono or combination therapy, wherein combination is administered as part of local Standard of Care and only one dose of each medication is administered within the allowable 10-hour window
2. Patients receiving palliative or hospice care, or those receiving limited interventional care.
3. Prisoners, mentally disabled, or unable to give consent. Should the patient not be able to provide informed consent the legally authorized representative can provide the consent on behalf of the patient.

4. Patients receiving experimental therapy or already enrolled in an interventional clinical trial in which a subject receives some type of intervention, which can include but is not limited to investigational drugs, medical devices, or vaccines.

   a. Subjects that are enrolled in non-interventional or observational clinical trials will be allowed to participate in this clinical trial.

5. Patients previously enrolled in the present clinical trial.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the diagnostic performance of HostDx Sepsis	Concordance of HostDx Sepsis bacterial readout with clinical adjudication	28 Days After Enrollment
Evaluation of the diagnostic performance of HostDx Sepsis	Concordance of HostDx Sepsis viral readout with clinical adjudication	28 Days After Enrollment
Evaluation of the prognostic performance of HostDx Sepsis	Concordance of HostDx Sepsis severity readout with receipt of ICU-level care (including requirement for ICU transfer, mechanical ventilation, vasopressors, or renal replacement therapy (RRT))	7 Days After Enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the prognostic performance of HostDx Sepsis	Concordance of HostDx Sepsis severity readout with receipt of ICU-level care (including requirement for ICU transfer, mechanical ventilation, vasopressors, or renal replacement therapy (RRT)) within 7 days OR 28-Day Hospital Mortality	28 Days after enrollment
Evaluation of the prognostic performance of HostDx Sepsis for 28-Day Hospital Mortality	Concordance of HostDx Sepsis severity readout with 28-Day Hospital Mortality	28 Days after enrollment

Collaborators and Investigators

• Sponsor: Inflammatix

Publications and helpful links

General Publications

• Gaieski DF, Mikkelsen ME, Band RA, Pines JM, Massone R, Furia FF, Shofer FS, Goyal M. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010 Apr;38(4):1045-53. doi: 10.1097/CCM.0b013e3181cc4824.
• Sweeney TE, Shidham A, Wong HR, Khatri P. A comprehensive time-course-based multicohort analysis of sepsis and sterile inflammation reveals a robust diagnostic gene set. Sci Transl Med. 2015 May 13;7(287):287ra71. doi: 10.1126/scitranslmed.aaa5993.
• Sweeney TE, Wong HR, Khatri P. Robust classification of bacterial and viral infections via integrated host gene expression diagnostics. Sci Transl Med. 2016 Jul 6;8(346):346ra91. doi: 10.1126/scitranslmed.aaf7165.
• Sweeney TE, Perumal TM, Henao R, Nichols M, Howrylak JA, Choi AM, Bermejo-Martin JF, Almansa R, Tamayo E, Davenport EE, Burnham KL, Hinds CJ, Knight JC, Woods CW, Kingsmore SF, Ginsburg GS, Wong HR, Parnell GP, Tang B, Moldawer LL, Moore FE, Omberg L, Khatri P, Tsalik EL, Mangravite LM, Langley RJ. A community approach to mortality prediction in sepsis via gene expression analysis. Nat Commun. 2018 Feb 15;9(1):694. doi: 10.1038/s41467-018-03078-2.
• Sweeney TE, Khatri P. Benchmarking Sepsis Gene Expression Diagnostics Using Public Data. Crit Care Med. 2017 Jan;45(1):1-10. doi: 10.1097/CCM.0000000000002021.
• Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
• Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, Artigas A, Schorr C, Levy MM. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014 Aug;42(8):1749-55. doi: 10.1097/CCM.0000000000000330.
• Singer M. Biomarkers in sepsis. Curr Opin Pulm Med. 2013 May;19(3):305-9. doi: 10.1097/MCP.0b013e32835f1b49.
• Coburn B, Morris AM, Tomlinson G, Detsky AS. Does this adult patient with suspected bacteremia require blood cultures? JAMA. 2012 Aug 1;308(5):502-11. doi: 10.1001/jama.2012.8262. Erratum In: JAMA. 2013 Jan 23;309(4):343.
• Mi MY, Klompas M, Evans L. Early Administration of Antibiotics for Suspected Sepsis. N Engl J Med. 2019 Feb 7;380(6):593-596. doi: 10.1056/NEJMclde1809210. No abstract available.
• Gunsolus IL, Sweeney TE, Liesenfeld O, Ledeboer NA. Diagnosing and Managing Sepsis by Probing the Host Response to Infection: Advances, Opportunities, and Challenges. J Clin Microbiol. 2019 Jun 25;57(7):e00425-19. doi: 10.1128/JCM.00425-19. Print 2019 Jul.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2020
• Primary Completion (Actual): August 6, 2024
• Study Completion (Actual): September 30, 2024

Study Registration Dates

• First Submitted: September 17, 2019
• First Submitted That Met QC Criteria: September 17, 2019
• First Posted (Actual): September 19, 2019

Study Record Updates

• Last Update Posted (Actual): October 22, 2024
• Last Update Submitted That Met QC Criteria: October 18, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Infection; C-Reactive Protein; Procalcitonin; mRNA; Lactate
• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Urogenital Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Infections; Communicable Diseases; Respiratory Tract Infections; Urinary Tract Infections; Toxemia; Intraabdominal Infections; Soft Tissue Infections; Meningitis; Encephalitis
• Other Study ID Numbers: INF-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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