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.

这项研究，新生儿肠病毒和人类副病毒病毒败血症：自然史和预测因子 发病率和死亡率是由医学博士Mark Abzug科学领导的。新生儿病毒败血症是一种临床综合征 以器官参与为特征，包括肝炎，凝血病（血小板减少） 有或没有凝结时间的混乱）和/或心肌炎，有时会与 脑膜脑炎或肺炎。尽管许多病毒会引起新生儿病毒败血症，包括 单纯疱疹病毒（HSV），巨细胞病毒（CMV）和腺病毒，最常见的两个原因是 肠病毒（EVS）和人类侧病毒（HPEVS）。新生儿EV或HPEV败血症的抗病毒治疗 是需要的，但尚未市售。新生儿病毒败血症的未来抗病毒试验的设计 从更好地理解这种严重但罕见的状况的自然历史将大大受益。 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 败血症，以及预测不良结果的临床和实验室参数的更好描述， 对于告知治疗试验的最佳设计非常重要，包括适当端点等问题， 样本量和纳入标准。定量PCR（QPCR）或其他实验室的潜在效用 目前，这些疾病中预测疾病，长期后遗症或死亡率严重程度的生物标志物是 未知。如果qPCR被证明是临床结果的有用预测指标或替代品，那么这可能会大大 促进治疗试验的性能。最后，迄今为止的研究表明一部分儿童 在临床上呈现新生儿病毒败血症没有EV，HPEV或其他已知病毒。这很重要 为了更好地理解使用病原体发现的最新工具的病因学剂。 拟议的研究旨在填补我们对新生儿病毒败血症的知识的差距 试验为这种疾病的预期抗病毒治疗疗法的发展。这将是 通过评估以下特定目的来完成：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），可预测新生儿EV的发病率和死亡率 新生儿HPEV败血症； 3）确定新生儿病毒败血症的病因不是由于EV，HPEV，HSV， CMV和腺病毒使用下一代测序进行病原体发现。系统的前瞻性 包括EV和HPEV败血症在内的新生儿病毒败血症的多中心评估将产生可以是的数据 用于未来第一阶段，II和III阶段治疗研究的抗病毒药物的设计 由Kyorin Pharmaceutical Co.，Ltd。和Vaxart，Inc。等制药公司制造的公司。