The aim of this project is to finish the development of an early, accurate and reliable in vitro diagnostic (IVD) test that identifies those severely injured trauma patient with systemic inflammatory response syndrome (SIRS) who will develop the sepsis pathology. The primary goals of this three year clinical assay development project are [1] to conduct a clinical study on 560 subjects, 360 trauma patients admitted to intensive care units (ICUs) at three regional trauma centers and 200 exempt """"""""unlinked, diagnostic specimens"""""""" from normal healthy blood donors after blood donation screening;and [2] to submit a De Novo 510(k) application to the USA FDA for regulatory clearance to market our IVD as an early and reliable test that can differentiate in trauma patients between SIRS due to inflammation from injury that isn't progressing to sepsis and SIRS that will deteriorate into the sepsis pathology. A clinical study which can be completed in 36 months or less will be conducted on our IVD test for plasma inducible nitric oxide synthase (iNOS) as an accurate and reliable plasma biomarker for detecting early the onset of sepsis in trauma patients by differentiating SIRS into two distinct types: one caused by injury which is not progressing to sepsis and the other which is progressing into sepsis with its associated heart, lung and kidney damage and dysfunction. Data gather during our previous clinical studies clearly demonstrate that a measurable increase in the plasma level of iNOS occurs early in the sepsis pathology (prior to organ damage and dysfunction) and that in plasma samples from normal healthy controls iNOS is either present at an extremely low concentration or completely absent. These clinical data provide a solid scientific basis for the utilization of iNOS as a new, specific, and early plasma biomarker for differentiating SIRS caused by inflammation from injury and SIRS that will progress into the life-threatening sepsis pathology. The next step in this IVD development project is to transition the test from the research laboratory onto the clinical lab market for widespread use which should allow for the earlier initiation of aggressive therapies that are currently delayed due to inadequate early prognosis/diagnosis. The delay in current Standard-of-Care treatment can result in heart, lung, kidney and other organ damage and dysfunction. The focus of this proposal is to gather the data needed to obtain FDA clearance to market our new IVD test by demonstrating in statistically significant numbers of trauma patients and healthy controls that the presence of iNOS in plasma can be used as a reliable early biochemical marker for the onset of the sepsis pathology. Based upon the estimated 7 million SIRS patients annually that can deteriorate into sepsis, an accurate and reliable IVD test could save 25,000 or more lives per year, and could significantly reduce the enormous long term healthcare cost of treating individuals who survive an episode of severe sepsis or septic shock. An approved clinical test that forecasts the onset of sepsis would be a major medical advance in fighting this life-threatening pathology.
Annually, more than 7 million people worldwide are affected by the hemodynamic, pulmonary and renal dysfunction associated with systemic inflammatory response syndrome (SIRS) that deteriorates into the sepsis pathology and causes more than 250,000 deaths per year in the USA and more than 750,000 worldwide. More people die each year from the organ dysfunction caused by this hyperinflammatory pathology than from stroke, lung cancer and breast cancer combined. Yet, there is no accurate and reliable clinical test available for the early detection of this life-threatening condition. In 2000, the Institute of Medicine of the National Academies of Science estimated the cost of the sepsis pathology to the US healthcare system to be $17 - 29 billion annually. Fast diagnosis and early treatment are essential to saving lives and reducing costs. Our candidate in vitro diagnostic (IVD) test can be used to differentiate trauma patients with SIRS from inflammation due to injury and those trauma patients with SIRS whose condition will deteriorate into sepsis with organ dysfunction, such as the heart, lung, and kidney dysfunction that are the hallmarks of the sepsis pathology. Data collected from our previous clinical studies show our IVD test can prognosticate the deterioration into sepsis 24 - 48 hours before the appearance of physiological symptoms. This project is focused on gathering the clinical data required to obtain FDA clearance by the De Novo 510(k) application process for a new clinical diagnostic test based upon our discovery of a plasma protein, plasma inducible nitric oxide synthase (iNOS), that is an early and specific biomarker that differentiates between SIRS from trauma and SIRS that will progress into the sepsis pathology with its associated organ damage and dysfunction.
