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Study never started, change in company focus on US
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NEWS2 score of 2-4 | Bio-sample collection |
| |
| NEWS2 score of 5-6 | Bio-sample collection |
| |
| NEWS2 score of ≥7 | Bio-sample collection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IMX-BVN-4 and IMX-SEV-4 | Diagnostic Test | Blood collection for mRNA analysis, Procalcitonin and CRP determination, molecular analysis of nasopharyngeal swab collection |
|
| 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 |
| 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 |
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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:
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:
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
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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)
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20048677 | Background | 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. | |
| 35467566 |
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| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D014552 | Urinary Tract Infections |
| D059413 | Intraabdominal Infections |
| D018461 | Soft Tissue Infections |
| D004660 | Encephalitis |
| D018805 | Sepsis |
| D007239 | Infections |
| ID | Term |
|---|---|
| D012140 | Respiratory Tract Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| 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 |
| 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. |
| 34166284 | 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. |
| 35819783 | 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. |
| 34671746 | 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. |
| 25972003 | 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. |
| 27384347 | 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. |
| 29449546 | 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. |
| 27681387 | 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. |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000090862 | Neuroinflammatory Diseases |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |