Clinical trial NCT05639504: Sepsis Prognosis and Diagnosis in the Emergency Department (SPEED)
Official title: Sepsis Prognosis and Diagnosis in the Emergency Department Using a Host Response Classifier (SPEED) UK - a Multi-Centre Observational Study
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
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
Lead sponsor: Inflammatix
Sponsor class: INDUSTRY
First posted: 2022-12-06
Enrollment: 0
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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)

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.

Eligibility criteria: 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

Primary outcomes:
measure: Primary Outcome 1
timeFrame: Admission
measure: Primary Outcome 2
timeFrame: Within 7 days after admission
Secondary outcomes:
measure: Secondary Outcome 1
timeFrame: Up to 28 days after admission
measure: Secondary Outcome 2
timeFrame: Admission
measure: Secondary Outcome 3
timeFrame: Within 7 days after admission
Other outcomes:
Locations:
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: 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.
citation: 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.
citation: 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.
citation: 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.
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.