Clinical trial NCT04094818: TriVerity in the Diagnosis and Prognosis of Emergency Department Patients With Suspected Infections and Suspected Sepsis
Official title: TriVerity in the Diagnosis and Prognosis of Emergency Department Patients With Suspected Infections and Suspected Sepsis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Respiratory Tract Infections
Urinary Tract Infections
Intra-Abdominal Infections
Skin and Soft Tissue Infection
Suspected Meningitis/Encephalitis or Any Other Infection
Sepsis
Keywords: Infection
mRNA
Procalcitonin
C-Reactive Protein
Lactate
Lead sponsor: Inflammatix
Sponsor class: INDUSTRY
First posted: 2019-09-19
Enrollment: 1441
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Evaluation of the diagnostic performance of HostDx Sepsis
timeFrame: 28 Days After Enrollment
measure: Evaluation of the diagnostic performance of HostDx Sepsis
timeFrame: 28 Days After Enrollment
measure: Evaluation of the prognostic performance of HostDx Sepsis
timeFrame: 7 Days After Enrollment
Secondary outcomes:
measure: Evaluation of the prognostic performance of HostDx Sepsis
timeFrame: 28 Days after enrollment
measure: Evaluation of the prognostic performance of HostDx Sepsis for 28-Day Hospital Mortality
timeFrame: 28 Days after enrollment
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama
state: Alabama
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Washington
country: United States
facility: Medstar Health Research Institute
state: District of Columbia
city: Jacksonville
country: United States
facility: University of Florida (UF) - Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Duluth
country: United States
facility: Essentia Institute of Rural Health
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Montclair
country: United States
facility: Hackensack Meridian Health
state: New Jersey
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Health
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Health
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: El Paso
country: United States
facility: Texas Tech University Health Sciences Center - El Paso
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Athens
country: Greece
facility: ATTIKON University Hospital
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: Singer M. Biomarkers in sepsis. Curr Opin Pulm Med. 2013 May;19(3):305-9. doi: 10.1097/MCP.0b013e32835f1b49.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.