Development of clinical triage assay for sepsis management in the Emergency Room

DESCRIPTION (provided by applicant): The overall project objective is to further develop and clinically validate an assay, SeptiCyte(R)Triage, to improve screening and early diagnosis of conditions associated with inflammation and sepsis in Emergency Room(ER). The test will deliver clinically relevant information on diagnosis, severity and broad pathogen category to better guide triage and therapeutic decisions in ER, and determine the aggressiveness of treatment required and ultimately assist in goal-oriented strategies for the management of severe sepsis and septic shock. Sepsis, an innate immune response to infection, is a growing problem worldwide with a high mortality rate. 17% of sepsis hospitalizations in the US end in death compared with only 2% ofother hospitalizations.. Sepsis can rapidly become life-threatening, and early aggressive and well-targeted treatment - when the patient first presents - increases the chance of survival. The majority of patients visiting ER with systemic inflammation haveundifferentiated Systemic Inflammatory Response Syndrome (SIRS). SIRS may have an infectious (sepsis) or non-infectious etiology (e.g. pancreatitis, ischemia, trauma and severe tissue injury). Sepsis and non-infectious SIRS present very similarly to the clinician and both are serious conditions. It is therefore critical that patients with suspected infection, or are at highrisk of infection, can be identified early in order to initiate evidence-based and goal-orientated medical therapy. In addition, distinguishing severity would provide new information to rapidly direct further investigations, target type of therapy, and determine the aggressiveness of treatment required. Earlier and more accurate information could reduce mortality, length of stay in intensive care and hospital, indiscriminate use of antibiotics, and development of antibiotic resistance. Asuragen will collaborate with ImmuneXpress to1) Identify genes that are differentially expressed and correlate with the diagnosis and severity of sepsis,2) Migrate the classifier signature from the microarray platform to qPCR, and 3) verify the classifier in an independent test set of specimens. This will result in fully specified predictive models to identif candidate biomarker panels that differentiate sepsis; and indicate the severity of sepsis. In Phase II, we will validate the singleplex qPCR assay on an independent and expanded data set from a large multi-site clinical trial, and migrate the SeptiCyte Triage assay to the Biocartis Apollo multiplex PCRplatform as a clinically useful, cost-effective tool that will aid in the rapi diagnostic evaluation of sepsis in the emergency care setting for guiding treatment and intervention. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Systemic inflammation can be caused by a variety of different causes, including bacterial, viral, and fungal infections (sepsis) as well as other causes. The goal of this project is to develop a rapid, point of care test that can distinguish between infectious and non-infectious systemic inflammation as well as the cause and severity of the response. This will serve a critical need by allowing physicians to choose the most appropriate and effective therapies, thereby improving survival and lowering the cost of treatment.