Sepsis Prognosis and Diagnosis in the Emergency Department (SPEED)

Study Overview
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Brief Summary
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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.

Detailed Description
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Study measurements consists of a blood collection via venepuncture into a PAXgene® Blood RNA tube (2.5 ml) and Na-Heparin tube (4 ml) normally within 1 hour of enrolment into the study. The samples will be stored and transferred in batches from recruiting centres to a core laboratory. The expression of 29 mRNAs contained in the IMX-BVN-4/SEV-4 classifier will be analysed to determine the likelihood of bacterial and viral infection, as well as the likelihood of clinical deterioration. A nasopharyngeal swab sample will also be obtained for participants with suspected respiratory tract infection. Clinical data collection will be recorded from source data using an electronic Case Report Form (eCRF) The diagnosis of infection will be confirmed by a clinical adjudication panel blinded to the ED and hospital discharge diagnosis for each case.

Official Title
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Sepsis Prognosis and Diagnosis in the Emergency Department Using a Host Response Classifier (SPEED) UK - a Multi-Centre Observational Study

Conditions
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Respiratory Tract Infections, Urinary Tract Infections, Intra-Abdominal Infections, Skin and Soft Tissue Infection, Suspected Meningitis/Encephalitis or Any Other Infection, Sepsis

Intervention / Treatment
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* Diagnostic Test: IMX-BVN-4 and IMX-SEV-4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| NEWS2 score of 2-4<br>Bio-sample collection | Diagnostic Test: IMX-BVN-4 and IMX-SEV-4<br>* Blood collection for mRNA analysis, Procalcitonin and CRP determination, molecular analysis of nasopharyngeal swab collection<br>|
| NEWS2 score of 5-6<br>Bio-sample collection | Diagnostic Test: IMX-BVN-4 and IMX-SEV-4<br>* Blood collection for mRNA analysis, Procalcitonin and CRP determination, molecular analysis of nasopharyngeal swab collection<br>|
| NEWS2 score of ≥7<br>Bio-sample collection | Diagnostic Test: IMX-BVN-4 and IMX-SEV-4<br>* Blood collection for mRNA analysis, Procalcitonin and CRP determination, molecular analysis of nasopharyngeal swab collection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcome 1 | Prognostic performance of IMX-SEV-4 using a composite endpoint of Receipt of critical-level care (including requirement for transfer to critical care, mechanical ventilation, vasopressors (>12 hours), or renal replacement therapy) within 7 days, and/or 28-day in-hospital mortality (sensitivity, specificity, likelihood ratios). | Up to 28 days after admission | 
| Secondary Outcome 2 | Diagnostic performance of the IMX-BVN-4 classifier in determining bacterial and viral infection compared with other biomarkers (procalcitonin and lactate) and clinical or laboratory findings obtained from standard of care, as compared to clinical adjudication (sensitivity, specificity, likelihood ratios). | Admission | 
| Secondary Outcome 3 | Prognostic performance of IMX-SEV-4 for clinical deterioration (NEWS2 of 5 or higher) within 7 days (sensitivity, specificity, likelihood ratios). | Within 7 days after admission | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infection, mRNA, host response