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

急诊室脓毒症管理临床分诊分析的开发

• 批准号: 8455392
• 负责人: Marie Ellen Fahey
• 金额: $ 31.44万
• 依托单位: ASURAGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2015-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8455392
• 关键词: Accident and Emergency department; Algorithms; Antibiotic Resistance; Antibiotics; Bacteria; Bacterial Infections; Bedside Testings; Bioinformatics; Biological Assay; Biological Markers; Budgets; Categories; Cessation of life; Clinical; Clinical Research; Data Set; Decision Making; Development; Diagnosis; Diagnostic; Early Diagnosis; Emergency Care; Emergency Situation; Etiology; Evaluation; Exons; Face; Failure; Fever; Genes; Goals; Health Care Costs; Hospitalization; Hospitals; Immune; Immune response; Incidence; Infection; Inflammation; Injury; Intensive Care; Interleukin-10; Intervention; Investigation; Ischemia; Legal patent; Length of Stay; Life; Measures; Medical; Messenger RNA; Molecular; Morbidity - disease rate; Multi-Institutional Clinical Trial; Mus; Mycoses; Noma; Pancreatitis; Patients; Performance; Pharmaceutical Preparations; Phase; Physicians; Sampling; Sepsis; Sepsis Syndrome; Septic Shock; Severities; Specific qualifier value; Specimen; System; TNF gene; Testing; Therapeutic; Time; Tissues; Training; Trauma; Treatment Cost; Treatment Protocols; Triage; Undifferentiated; Virus Diseases; Visit; base; clinically relevant; cost; cost effective; effective therapy; evidence base; improved; meetings; microbial; mortality; novel strategies; pathogen; point of care; predictive modeling; product development; public health relevance; response; screening; tool

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% of other 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 have undifferentiated 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 PCR platform 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.

描述（由申请方提供）：总体项目目标是进一步开发和临床验证一种检测方法SeptiCyte（R）Triage，以改善急诊室（ER）中炎症和脓毒症相关疾病的筛查和早期诊断。该测试将提供有关诊断，严重程度和广泛病原体类别的临床相关信息，以更好地指导ER的分诊和治疗决策，并确定所需治疗的积极性，并最终协助以目标为导向的策略管理严重脓毒症和脓毒性休克。脓毒症是一种对感染的先天免疫反应，是全球范围内日益严重的问题，死亡率很高。在美国，17%的败血症住院患者最终死亡，而其他住院患者的这一比例仅为2%。脓毒症可以迅速成为危及生命的，早期积极和有针对性的治疗-当病人第一次出现-增加生存的机会。大多数患有全身性炎症的ER患者患有未分化的全身炎症反应综合征（SIRS）。SIRS可能具有感染性（败血症）或非感染性病因（例如胰腺炎、缺血、创伤和严重组织损伤）。脓毒症和非感染性SIRS与临床医生非常相似， 严重的条件。因此，至关重要的是，可以及早发现疑似感染或感染高危患者，以便启动循证和目标导向的医学治疗。此外，区分严重程度将提供新的信息，以快速指导进一步的调查，目标类型的治疗，并确定所需的治疗的侵略性。更早和更准确的信息可以减少死亡率、重症监护和住院时间、滥用抗生素和抗生素耐药性的发展。Asuragen将与ImmuneXpress合作，以1）识别差异表达的基因，并与脓毒症的诊断和严重程度相关，2）将分类器签名从微阵列平台迁移到qPCR，3）在独立的样本测试集中验证分类器。这将产生完全指定的预测模型，以鉴定区分脓毒症的候选生物标志物组;并指示脓毒症的严重程度。在第II阶段，我们将在来自大型多中心临床试验的独立和扩展数据集上验证单重qPCR检测，并将SeptiCyte Triage检测迁移到Biocartis Apollo多重PCR平台，作为临床上有用的、具有成本效益的工具，有助于在急诊护理环境中对脓毒症进行快速诊断评价，以指导治疗和干预。