ObsErvational Study of the Practical Cinical UTility of the NuQ.® H3.1 Nucleosome Levels in Adult Patients With Sepsis to Facilitate Early Diagnosis and Prognostication. (EPICETUS)

Study Overview
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Brief Summary
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This is a study to evaluate the diagnostic performance of the investigation NuQ. (R) H3.1 nucleosome assay as a diagnostic marker of sepsis in a population of patients admitted to critical care with signs suspicious of infection and consistent with the sepsis 3 definition. These patients will be compared to a group of adult surgical patients free from infection that are undergoing their first cardiac surgery.

Detailed Description
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This is a single centre, prosepctive study to evaluate the diagnostic performance of the investigation NuQ. (R) H3.1 nucleosome assay as a diagnostic marker of sepsis in a population of patients admitted to critical care with signs suspicious of infection and consistent with the sepsis 3 definition. The H3.1 assay is a chemiluminescent sandwich immunoassay for the detection of nucleosomes circulating in human plasma. The test quantifies the level of circulating nucleosomes and in conjunction with other laboratory findings and clinical assessment aids in the early detection of sepsis with organ dysfunction.

Official Title
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ObsErvational Study of the Practical Cinical UTility of the NuQ.® H3.1 Nucleosome Levels in Adult Patients With Sepsis to Facilitate Early Diagnosis and Prognostication. (EPICETUS)

Conditions
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Sepsis

Intervention / Treatment
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* Diagnostic Test: NuQ H3.1 Nucleosome Assay


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be at least 18 years of age to be included in the study. Patients must have been admitted to critical care emergently with signs and symptoms consistent with a possible diagnosis of sepsis: defined as one of these types of infections: respiratory system, renal and genito-urinary system, gastrointestinal and intra-abdominal system, central nervous system, musculoskeletal, sepsis or fever of unknown origin A 'comparator' arm will be included of patients aged over 18yrs of age undergoing planned elective coronary artery bypass graft surgery with anticipated post-operative care in critical care unit Exclusion Criteria: Any subject not meeting the criteria above. Patients who are re-admitted to intensive care unit within the same hospital admission The exclusion criteria are designed to remove confounding effects from concomitant conditions that may render the interpretation of the NuQ.® H3.1 assay impossible. These circumstances are few, but exclusions will include patients with limitations of care, including 'Do not attempt resuscitation' orders. Patients with severe anaemia (as defined by a Hb<50g/dL) will be excluded. Subjects with any other severe concurrent disease that, in the judgment of the Principal Investigator, would make the subject inappropriate for entry into this study. Patients in the 'comparator' arm who are undergoing cardiac surgery will be excluded if they have an active infection and specifically patients with a suspected or confirmed diagnosis of infective endocarditis. Any patient undergoing cardiac surgery with a condition that might influence their immune response will be excluded. These include but are not limited to uncontrolled HIV, AIDS, uncontrolled systemic lupus erythematosus, rheumatoid arthritis or mixed connective tissue disorder, previous cancer and previous treatment with chemotherapy or the recipient of a solid organ or bone marrow transplant.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sepsis<br>Adult patients admitted to critical care with a presumed diagnosis of sepsis. | Diagnostic Test: NuQ H3.1 Nucleosome Assay<br>* Serial analysis on whole blood of nucleosome levels until resolution of sepsis or discharge.<br>|
| Cardiac surgery<br>Adult cardiac surgery patients that are free from infection undergoing their first cardiac surgery. | Diagnostic Test: NuQ H3.1 Nucleosome Assay<br>* Serial analysis on whole blood of nucleosome levels until resolution of sepsis or discharge.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the levels of H3.1 nucleosomes in critically ill patients diagnosed with sepsis. | To investigate the levels of H3.1 nucleosomes in critically ill patients diagnosed with sepsis or septic shock (as defined by Sepsis-3 criteria at time of presentation), specifically to monitor how these levels change over time in relation to disease progression, clinical data and other routinely collected biomarkers such as CRP and procalcitonin. | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the potential utility of levels of NETs/Cf DNA (as measured by the H3.1 nucleosome assay) as a companion diagnostic test of septic shock, disease monitoring, severity and prognosis. |  | 90 days |