Sepsis Prognosis and Diagnosis in the Emergency Department (SPEED)

Withdrawn

• Conditions: Urinary Tract Infections; Skin and Soft Tissue Infection; Respiratory Tract Infections; Intra-Abdominal Infections; Sepsis; Suspected Meningitis/Encephalitis or Any Other Infection
• Interventions: Diagnostic Test: IMX-BVN-4 and IMX-SEV-4

• Registration Number: NCT05639504
• Lead Sponsor: Inflammatix

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2022-09-27
• Study First Submitted QC: 2022-11-28
• Study Start: 2022-12
• Study First Posted: 2022-12-06
• Primary Completion: 2023-04
• Study Completion: 2023-05
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-21
• Last Update Posted: 2023-12-27

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Adult participants (16 years and older) presenting to the ED (or related assessment and treatment facilities such as SDEC or AMU) with:

1. Clinically suspected infection of any aetiology as the reason for attendance; AND
2. NEWS2 score of ≥2 (any dimension, using latest score)

Exclusion Criteria

1. 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

2. 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

3. Prisoners or those in police custody

4. Patients who permanently lack the capacity to give informed consent

5. Previously enrolled in SPEED UK study

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
NEWS2 score of ≥7	IMX-BVN-4 and IMX-SEV-4	Bio-sample collection
NEWS2 score of 5-6	IMX-BVN-4 and IMX-SEV-4	Bio-sample collection
NEWS2 score of 2-4	IMX-BVN-4 and IMX-SEV-4	Bio-sample collection

Primary Outcome Measures

Name	Time	Method
Primary Outcome 1	Admission	Performance of the host response classifier IMX-BVN-4 to diagnose bacterial and viral infection as compared to clinical adjudication (sensitivity, specificity, likelihood ratios).
Primary Outcome 2	Within 7 days after admission	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).

Secondary Outcome Measures

Name	Time	Method
Secondary Outcome 1	Up to 28 days after admission	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).
Secondary Outcome 2	Admission	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).
Secondary Outcome 3	Within 7 days after admission	Prognostic performance of IMX-SEV-4 for clinical deterioration (NEWS2 of 5 or higher) within 7 days (sensitivity, specificity, likelihood ratios).