Clinical Study on Inos Elisa for Sepsis and Septic Shock

Period of Performance: 09/30/1999 - 03/31/2000

Unknown

Phase 1 SBIR

Recipient Firm

Research and Diagnostic Antibodies
North Las Vegas, NV 89032
Principal Investigator

Abstract

We initially proposed and then subsequently found during a pilot clinical study that a measurable increase in the circulating level of human inducible nitric oxide synthase (hiNOS) occurs during an episode of systemic inflammatory response syndrome (SIRS) or sepsis prior to the onset of severe sepsis and septic shock. Our goal is to develop immunoassays for clinical use that can rapidly detect, quantitate and monitor this increase in hiNOS prior to the onset of severe sepsis and septic shock, and thus provide an early warning signal for future deleterious events. An early diagnosis will provide a basis for an earlier initiation of therapies than is currently practiced. To achieve our goal, we have developed a highly specific sandwich ELISA for hiNOS based upon our panel of twenty anti-hiNOS monoclonal antibodies. The ELISA and three other confirmatory immunoassays that we developed for hiNOS have been used to detect and measure the level of hiNOS in peripheral blood monocytes (PBMC) during an pilot clinical study on a cohort of 10 ICU patients. The results obtained from this pilot study indicate that an increased level of hiNOS in PBMC can be measured and may be a good biochemical marker that can be used to prognosticate the onset of severe sepsis and septic shock. The aim of this phase I project is to extend the clinical study to a larger number of patients in order to assess if the observations made during the pilot clinical study to a larger number of patients in order to assess if the observations made during the pilot clinical study are generally applicable. Once completed, the overall project will bring a needed new clinical diagnostic onto the marker, and this, in turn, will lead to improved health care for critically ill patients. PROPOSED COMMERCIAL APPLICATION: Over 1,200,000 cases/year of systemic inflammatory response syndrome and sepsis occur in the USA; these lead to over 500,000 cases/year of severe sepsis and septic shock and 100,000-250,000 deaths/year. A rapid test to assess a patient's entry into and progress down the sepsis pathway to severe sepsis and septic shock is needed. Our immunoassays are designed to meet this clinical need, to lower patient cost by reducing the length of ICU stays, and to improve patient outcome.