CLINICAL STUDY ON INOS ELISA FOR SEPSIS AND SEPTIC SHOCK

INOS ELISA 治疗败血症和败血性休克的临床研究

• 批准号: 6017137
• 负责人: ROBERT J WEBBER
• 金额: $ 9.98万
• 依托单位: RESEARCH AND DIAGNOSTIC ANTIBODIES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6017137
• 关键词: bacterial disease; blood toxicology; clinical research; diagnosis design /evaluation; early diagnosis; enzyme induction /repression; enzyme linked immunosorbent assay; human subject; monoclonal antibody; monocyte; nitric oxide synthase; prognosis; septic shock

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.

我们最初提出，随后在一项试点临床研究中发现，在严重败血症和败血性休克发作之前，在全身炎症反应综合征 (SIRS) 或败血症发作期间，人诱导型一氧化氮合酶 (hiNOS) 的循环水平会出现可测量的增加。我们的目标是开发用于临床的免疫测定法，能够在严重败血症和败血性休克发作之前快速检测、定量和监测 hiNOS 的增加，从而为未来的有害事件提供早期预警信号。早期诊断将为比目前实践更早开始治疗提供基础。为了实现我们的目标，我们基于 20 种抗 hiNOS 单克隆抗体，开发了一种针对 hiNOS 的高度特异性夹心 ELISA。在一项针对 10 名 ICU 患者的试点临床研究中，我们为 hiNOS 开发的 ELISA 和其他三种验证性免疫测定法已用于检测和测量外周血单核细胞 (PBMC) 中的 hiNOS 水平。这项初步研究的结果表明，可以测量 PBMC 中 hiNOS 水平的升高，并且可能是一个很好的生化标志物，可用于预测严重脓毒症和脓毒性休克的发生。该第一阶段项目的目的是将临床研究扩展到更多的患者，以评估试点临床研究期间的观察结果是否适用于更多的患者，从而评估试点临床研究期间的观察结果是否普遍适用。一旦完成，整个项目将为标记带来所需的新临床诊断，这反过来将改善危重患者的医疗保健。拟议的商业应用：美国每年发生超过 1,200,000 例全身炎症反应综合征和脓毒症；这些导致每年超过 500,000 例严重脓毒症和感染性休克病例，以及每年 100,000-250,000 例死亡。需要一种快速测试来评估患者是否进入败血症并进展为严重败血症和败血性休克。我们的免疫测定旨在满足这种临床需求，通过减少 ICU 住院时间来降低患者成本，并改善患者治疗结果。