Sepsis Prognosis and Diagnosis in the Emergency Department (SPEED)

NCT05639504 | Withdrawn

• 1 other identifier: INF-25
• Study Type: observational
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to evaluate the diagnostic and prognostic performance of a novel mRNA diagnostic/prognostic classifier (interprets the expression of 29 host response mRNA biomarkers) from whole blood in adult patients presenting to emergency departments (ED) with suspected infection.

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; host response

Outcome Measures

Primary Outcomes (2)

• Primary Outcome 1

  Performance of the host response classifier IMX-BVN-4 to diagnose bacterial and viral infection as compared to clinical adjudication (sensitivity, specificity, likelihood ratios).

  Admission

• Primary Outcome 2

  Prognostic performance of IMX-SEV-4 using an endpoint of receipt of critical-level care (including requirement for admission to critical care, mechanical ventilation, vasopressors (\>12 hours), or renal replacement therapy) within 7 days (sensitivity, specificity, likelihood ratios).

  Within 7 days after admission

Secondary Outcomes (3)

• Secondary Outcome 1

  Up to 28 days after admission

• Secondary Outcome 2

  Admission

• Secondary Outcome 3

  Within 7 days after admission

Study Arms (3)

NEWS2 score of 2-4

Bio-sample collection

Diagnostic Test: IMX-BVN-4 and IMX-SEV-4

NEWS2 score of 5-6

Bio-sample collection

Diagnostic Test: IMX-BVN-4 and IMX-SEV-4

NEWS2 score of ≥7

Bio-sample collection

Diagnostic Test: IMX-BVN-4 and IMX-SEV-4

Interventions

IMX-BVN-4 and IMX-SEV-4 DIAGNOSTIC_TEST

Blood collection for mRNA analysis, Procalcitonin and CRP determination, molecular analysis of nasopharyngeal swab collection

NEWS2 score of 2-4; NEWS2 score of 5-6; NEWS2 score of ≥7

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult participants (16 years and older) presenting to the ED (or related assessment and treatment facilities such as SDEC or AMU) with clinically suspected infection of any aetiology as the reason for attendance and a NEWS2 score of ≥2 (any dimension, using latest score)

You may qualify if:

• Adult participants (16 years and older) presenting to the ED (or related assessment and treatment facilities such as SDEC or AMU) with:
• Clinically suspected infection of any aetiology as the reason for attendance; AND
• NEWS2 score of ≥2 (any dimension, using latest score)

You may not qualify if:

• Treatment with systemic antibiotics, systemic antiviral agents or systemic antifungal agents within the past 7 days prior to the ED visit. Participants will not be excluded for use of:
• Antiviral treatment for HIV infection and hepatitis B and hepatitis C
• Topical antibiotics, topical antiviral or topical antifungal agents
• Anti-herpes prophylaxis aiding suppression of a recuring herpes infection
• Peri-operative (prophylactic) antibiotics
• A single dose of antimicrobials during the present ED visit; 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
• Presence of an advance directive to withhold life-sustaining treatment or a clear plan in place to that effect (ie. an explicit decision by patient/family/carer in conjunction with clinical team that active treatment beyond symptomatic relief is not appropriate). Note that patients who do not wish to receive cardiopulmonary resuscitation (CPR) but active treatment is still indicated may still qualify for entry into study
• Prisoners or those in police custody
• Patients who permanently lack the capacity to give informed consent
• Previously enrolled in SPEED UK study

Sponsors & Collaborators

• Inflammatix: lead

Related Publications (9)

• 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.

  PMID: 20048677 BACKGROUND

• Galtung N, Diehl-Wiesenecker E, Lehmann D, Markmann N, Bergstrom WH, Wacker J, Liesenfeld O, Mayhew M, Buturovic L, Luethy R, Sweeney TE, Tauber R, Kappert K, Somasundaram R, Bauer W. Prospective validation of a transcriptomic severity classifier among patients with suspected acute infection and sepsis in the emergency department. Eur J Emerg Med. 2022 Oct 1;29(5):357-365. doi: 10.1097/MEJ.0000000000000931. Epub 2022 Apr 21.

  PMID: 35467566 BACKGROUND

• Bauer W, Kappert K, Galtung N, Lehmann D, Wacker J, Cheng HK, Liesenfeld O, Buturovic L, Luethy R, Sweeney TE, Tauber R, Somasundaram R. A Novel 29-Messenger RNA Host-Response Assay From Whole Blood Accurately Identifies Bacterial and Viral Infections in Patients Presenting to the Emergency Department With Suspected Infections: A Prospective Observational Study. Crit Care Med. 2021 Oct 1;49(10):1664-1673. doi: 10.1097/CCM.0000000000005119.

  PMID: 34166284 BACKGROUND

• Brakenridge SC, Chen UI, Loftus T, Ungaro R, Dirain M, Kerr A, Zhong L, Bacher R, Starostik P, Ghita G, Midic U, Darden D, Fenner B, Wacker J, Efron PA, Liesenfeld O, Sweeney TE, Moldawer LL. Evaluation of a Multivalent Transcriptomic Metric for Diagnosing Surgical Sepsis and Estimating Mortality Among Critically Ill Patients. JAMA Netw Open. 2022 Jul 1;5(7):e2221520. doi: 10.1001/jamanetworkopen.2022.21520.

  PMID: 35819783 BACKGROUND

• Brakenridge SC, Starostik P, Ghita G, Midic U, Darden D, Fenner B, Wacker J, Efron PA, Liesenfeld O, Sweeney TE, Moldawer LL. A Transcriptomic Severity Metric That Predicts Clinical Outcomes in Critically Ill Surgical Sepsis Patients. Crit Care Explor. 2021 Oct 14;3(10):e0554. doi: 10.1097/CCE.0000000000000554. eCollection 2021 Oct.

  PMID: 34671746 BACKGROUND

• 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.

  PMID: 25972003 BACKGROUND

• 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.

  PMID: 27384347 BACKGROUND

• 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.

  PMID: 29449546 BACKGROUND

• 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.

  PMID: 27681387 BACKGROUND

MeSH Terms

Conditions

Respiratory Tract Infections; Urinary Tract Infections; Intraabdominal Infections; Soft Tissue Infections; Encephalitis; Sepsis; Infections

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2022
• First Posted: December 6, 2022
• Study Start: December 1, 2022
• Primary Completion: April 1, 2023
• Study Completion: May 1, 2023
• Last Updated: December 27, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share