None listed
Conditions
Brief summary
Sepsis is a specific systemic inflammatory response to either a gram positive or gram negative bacterial or fungal infection. The cornerstone of sepsis diagnosis and prognosis for many decades has been identifying the causative circulating pathogen and quantitating single blood analytes to assess the patient’s physiological response to the pathogen. However, it is an individual’s immune system, which determines clinical escalation to septic shock and not the causative pathogen. Given that the immune response is complex and multifactorial there is a necessity for an assay that can expedite the early diagnosis of sepsis, as well as evaluate the individual’s response to therapy/management. Recent developments in biomolecular technologies using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) enable gene expression patterns to be translated into diagnostic pathology profiles and have the capacity to improve acute clinical management. “Athlomics” development has characterised a panel of 42 inflammatory gene expression biomarkers that significantly correlate with incidence of sepsis using both equine and human models. Athlomics preliminary outcomes, using data sets from local clinical trials, suggest that this investigational diagnostic has a better than 95% accuracy of detecting sepsis in patients admitted to a tertiary clinical setting with an acute non-specific immunoinflammatory response, based on area under the curve calculations using receiver operator characteristics (ROC) analyses. This is an important finding, and indicates that the specificity of the Athlomics sepsis signature is well within the performance band required for clinical use. To improve the strength of this signal Gene Expression Omnibus (GEO) samples were compared with gene expression profiles from the sepsis cohort, demonstrating a specificity of greater than 99% based on ROC curves. The Athlomics sepsis signature was applied to all currently available GEO Genechip data for human whole blood studies and a subset of 168 control samples, including both healthy controls and controls with known conditions not expected to produce inflammatory signals. These outcomes, suggest that this assay is robust and has the capacity to be used in future clinical practice for the definitive diagnosis of sepsis. Moreover, it has the potential to be used in the practice of ‘personalised’ medicine, where an individual’s gene expression signature can be used to structure a specific clinical management plan, determine response to therapy and provide prognostic updates
Interventions
SeptiCyte Lab is a diagnostic that uses a panel of 42 molecular (gene expression) biomarkers to distinguish sepsis from other non-infectious inflammatory conditions. For the purposes of this trial it will be used to monitor patients with severe sepsis or septic shock, over a 10-day period and while in the intensive care unit, to establish immune status. This test will be conducted using ribonucleic acid (RNA) isolated from 5ml of arterial or venous blood. Blood draws will be taken on Days 1,
SeptiCyte Lab is a diagnostic that uses a panel of 42 molecular (gene expression) biomarkers to distinguish sepsis from other non-infectious inflammatory conditions. For the purposes of this trial it will be used to monitor patients with severe sepsis or septic shock, over a 10-day period and while in the intensive care unit, to establish immune status. This test will be conducted using ribonucleic acid (RNA) isolated from 5ml of arterial or venous blood. Blood draws will be taken on Days 1, 2, 3, 5, 7 and 10 during this clinical trial.
Sponsors
ImmuneXpress Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Diagnosis
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged over 18 years 2. Body Mass Index < 40 3. Clinical signs and symptoms of severe sepsis or septic shock. In brief, patients must be admitted to the intensive care unit with two or more signs of systemic inflammation within the last 24 hours, with a proven or suspected source of infection and the sepsis-induced dysfunction of at least one organ or system. The absence of positive culture results will not affect clinical diagnosis of sepsis. Systemic Inflammatory Response (SIRS) Criteria: temperature >38°C or <36°C; heart rate >90 beats/min; respiratory rate >20 breathes/min or a partial pressure of carbon dioxide (PaCO2) of <4.3 kPa (<32 mm Hg) or mechanical ventilation; and a white blood cell count <4,000 cells/mm3 (<4 x 109 cells/L) or >12,000 cells/mm3 (>12 x 109 cells/L) or >10% immature neutrophils (band forms). (Consensus from the American College of Chest Physicians/ Society of Critical Care Medicine) Infection Criteria: evidence of proven or suspected infection as demonstrated by one or more of the following: white cells in a normally sterile body fluid; perforated viscus; radiographic evidence of pneumonia in association with the production of purulent sputum; a syndrome related to a high risk of infection Organ/System Dysfunction Criteria: Cardiovascular – systolic arterial blood pressure of less than or equal to 90 mmHg or mean arterial pressure of less than or equal to 70 mmHg for >1 hr, despite adequate fluid resuscitation, adequate intravascular volume status or the use of vasopressors in an attempt to maintain a systolic pressure of greater than or equal to 90 mmHg or a mean arterial pressure of greater than or equal to 70 mmHg; Pulmonary – partial pressure of arterial oxygen/inspired oxygen (PaO2/FiO2 ratio) less than or equal to 250 in the presence of other dysfunctional organs or systems or less than or equal to 200 if the lung is the only dysfunctional organ; Renal – urine output of <0.5 ml/kg of body weight/ hr for 1 hour, despite adequate fluid resuscitation; Unexplained Metabolic Acidosis – pH less than or equal to 7.30 or a base deficit of greater than or equal to 5.0 mmol/L in association with a plasma lactate level that is >1.5 times the upper limit of the local laboratory reference range Haematologic – platelet count <80,000/mm3 (<80,000 microlitres), or platelet count has decreased by 50% in the 3 days preceding enrolment. 4. The patient and substitute health authority are fluent in English (both written and spoken) and the patient or substitute health authority are capable of providing informed consent to participate in the study
Exclusion criteria
1. Patients who have an autoimmune disease or other documented chronic immunological disorder e.g. systemic lupus erythmatosus (SLE), Crohn’s disease, rheumatoid arthritis, multiple sclerosis (MS), Type 1 Diabetes Mellitus 2. Oncology patients receiving chemotherapy within the last 3 months 3. Solid-organ transplant recipients
Outcome results
None listed