EV Sepsis Natural History

EV脓毒症自然史

• 批准号: 10465119
• 负责人: DAVID W KIMBERLIN
• 金额: $ 25.58万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10465119
• 关键词: Activated Partial Thromboplastin Time measurement; Adenoviruses; Alanine Transaminase; Antiviral Agents; Aspartate Transaminase; Bilirubin; Biological Markers; Blood; Blood Coagulation Disorders; Blood Urea Nitrogen; Blood specimen; California; Case Series; Child; Circulation; Clinical; Clinical Research; Coagulation Process; Creatinine; Cytomegalovirus; Data; Development; EFRAC; Echocardiography; Enrollment; Ensure; Enterovirus; Etiology; Fibrin fragment D; Funding; Future; Hematocrit procedure; Hemoglobin; Hepatitis; Human; Infant; Infection; Knowledge; Laboratories; Life; Literature; Meningoencephalitis; Methodology; Molecular Diagnostic Testing; Morbidity - disease rate; Myocarditis; Natural History; Neonatal; Neonatal Mortality; Organ; Outcome; Parechovirus; Pattern; Performance; Perinatal Infection; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Platelet Count measurement; Polymerase Chain Reaction; Population; Prothrombin time assay; Publishing; Pulmonary Inflammation; Rare Diseases; Recording of previous events; Sample Size; San Francisco; Seasons; Sepsis; Severity of illness; Shortening Fraction; Simplexvirus; Specimen; Survivors; Syndrome; Technology; Therapeutic Trials; Thrombocytopenia; United States; United States Food and Drug Administration; United States National Institutes of Health; Universities; Viral; Viral Load result; Viremia; Virus; White Blood Cell Count procedure; adverse outcome; antiviral drug development; clinical trial readiness; congenital infection; design; efficacy study; experience; follow-up; improved; improved outcome; inclusion criteria; interest; long-term sequelae; mortality; neonatal human; neonate; next generation sequencing; novel; pathogen; population based; prospective; tool; trial readiness; viral detection

This study, Neonatal Enterovirus and Human Parechovirus Viral Sepsis: Natural History and Predictors of Morbidity and Mortality, is scientifically led by Mark Abzug, MD. Neonatal viral sepsis is a clinical syndrome characterized by a constellation of organ involvement that includes hepatitis, coagulopathy (thrombocytopenia with or without derangement of clotting times), and/or myocarditis, sometimes occurring in concert with meningoencephalitis or pneumonitis. Although a number of viruses can cause neonatal viral sepsis, including herpes simplex virus (HSV), cytomegalovirus (CMV), and adenovirus, two of the most frequent causes are enteroviruses (EVs) and human parechoviruses (HPeVs). Antiviral treatment for neonatal EV or HPeV sepsis is needed, but not yet commercially available. The design of future antiviral trials for neonatal viral sepsis would greatly benefit from a better understanding of the natural history of this serious, but rare, condition. More precise definition of rates of long-term morbidity and mortality associated with neonatal EV and HPeV sepsis, and better delineation of clinical and laboratory parameters that are predictive of adverse outcomes, are important to inform the optimal design of therapeutic trials, including issues such as appropriate endpoints, sample size, and inclusion criteria. The potential utility of quantitative PCR (qPCR) or other laboratory biomarkers to predict severity of illness, long-term sequelae, or mortality in these illnesses is currently unknown. If qPCR was shown to be a useful predictor of or surrogate for clinical outcomes, this could greatly facilitate the performance of therapeutic trials. Finally, studies to date suggest that a portion of children presenting clinically with neonatal viral sepsis do not have EVs, HPeVs, or other known viruses. It is important to better understand the full spectrum of etiologic agents using state-of-the-art tools for pathogen discovery. The proposed study is designed to fill in these gaps in our knowledge about neonatal viral sepsis to advance trial readiness for the anticipated development of antiviral treatment therapy for this condition. This will be accomplished by evaluating the following specific aims: 1) to estimate the morbidity and mortality rates of neonatal EV sepsis and neonatal HPeV sepsis; 2) to identify clinical and laboratory parameters, including quantitative polymerase chain reaction (qPCR), predictive of morbidity and mortality from neonatal EV and neonatal HPeV sepsis; and 3) to determine the etiologies of neonatal viral sepsis not due to EV, HPeV, HSV, CMV, and adenovirus using next-gen sequencing for pathogen discovery. The systematic prospective multicenter assessment of neonatal viral sepsis, including EV and HPeV sepsis, will produce data that can be used in the design of future Phase I, II, and III treatment studies with antiviral drugs currently in development by pharmaceutical companies, such as KYORIN Pharmaceutical Co., Ltd., and Vaxart, Inc.

新生儿肠道病毒和人类副肠孤病毒病毒性脓毒症：自然史和 Mortality and Mortality，由Mark Abzug博士领导。新生儿病毒性败血症是一种临床综合征 以包括肝炎、凝血病（血小板减少症）在内的一系列器官受累为特征 有或没有凝血时间紊乱），和/或心肌炎，有时与 脑膜脑炎或肺炎。尽管许多病毒可引起新生儿病毒性败血症，包括 单纯疱疹病毒（HSV）、巨细胞病毒（CMV）和腺病毒，两种最常见的原因是 肠道病毒（EV）和人双埃柯病毒（HPeV）。新生儿EV或HPeV败血症的抗病毒治疗 是需要的，但还没有商业化。新生儿病毒性脓毒症未来抗病毒试验的设计 如果能更好地了解这种严重但罕见的疾病的自然史，将大大受益。 与新生儿EV和HPeV相关的长期发病率和死亡率的更精确定义 脓毒症，以及更好地描述预测不良结局的临床和实验室参数， 对于指导治疗试验的最佳设计很重要，包括适当的终点等问题， 样本量和入选标准。定量PCR（qPCR）或其他实验室技术的潜在效用 生物标志物来预测疾病的严重程度，长期后遗症，或死亡率在这些疾病是目前 未知如果qPCR被证明是一个有用的预测或替代临床结果，这将大大 促进治疗试验的进行。最后，迄今为止的研究表明，一部分儿童 临床上表现为新生儿病毒性败血症的患者没有EV、HPeV或其他已知病毒。重要的是 使用最先进的病原体发现工具更好地了解病原体的全谱。 这项拟议的研究旨在填补我们对新生儿病毒性脓毒症的知识空白， 试验准备为预期的发展抗病毒治疗治疗这种情况。这将是 通过评估以下具体目标来实现：1）估计 新生儿EV败血症和新生儿HPeV败血症; 2）确定临床和实验室参数，包括 定量聚合酶链反应（qPCR），预测新生儿EV的发病率和死亡率， 新生儿HPeV脓毒症;和3）确定新生儿病毒性脓毒症的病因，其不是由于EV，HPeV，HSV， CMV和腺病毒使用下一代测序用于病原体发现。系统的前瞻性 新生儿病毒性败血症（包括EV和HPeV败血症）的多中心评估将产生可用于 用于设计目前正在开发的抗病毒药物的未来I、II和III期治疗研究 由KYORIN Pharmaceutical Co.等制药公司，有限公司、和Vaxart，Inc.