Direct from blood identification of bloodstream infections in newborns

直接从血液中鉴定新生儿血流感染

基本信息

批准号：
10477151
负责人：
Alon Singer
金额：
$ 99.46万
依托单位：
HELIXBIND, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10477151
关键词：
Accounting Address Adopted Adult Affect Antibiotics Antimicrobial Resistance Biological Assay Birth Blood Blood Volume Blood specimen Budgets Chicago Childhood Clinic Clinical Clinical Microbiology Clinical Research Clinical assessments Communicable Diseases DNA sequencing Data Detection Development Devices Diagnosis Diagnostic Diagnostic Equipment Diagnostic tests Disease Early Diagnosis Ensure Etiology Evidence based treatment Exhibits Feedback Hospitals Hour Infection Intervention Laboratories Life Live Birth Medical center Methods Molecular Morbidity - disease rate Neonatal Mortality Newborn Infant Outcome Patients Pediatric Hospitals Performance Phase Population Positioning Attribute Preparation Process Regulatory Pathway Resistance Risk Sampling Sensitivity and Specificity Sepsis Specificity Stress System Technology Temperature Testing Time TimeLine University Hospitals Whole Blood Work accurate diagnosis antimicrobial assay development base cost cross reactivity design diagnostic assay diagnostic platform diagnostic strategy experience in-vitro diagnostics innovation instrument instrumentation intrapartum manufacturing scale-up meetings member microbial microbiome mortality neonatal sepsis neonate outcome prediction pathogen pathogenic bacteria pathogenic fungus patient population performance tests product development programs resistance gene side effect success systemic inflammatory response

项目摘要

PROJECT SUMMARY Neonatal sepsis is a life-threatening disease that affects 2 out of every 1,000 live births in the US. Caused by an invasive bloodstream infection (BSI) occurring either at the time of birth or soon thereafter, the disease’s initial clinical manifestations are often non-specific, variable, at times subtle, and often common to signs of stress. Early diagnosis followed by appropriate antimicrobial intervention is a key predictor of outcomes. Selection of appropriate antimicrobials is limited by the current diagnostic process for detection and identification of BSIs which all rely on primary blood cultures. Cultures are slow, often requiring days to yield a result, and prone to false-negatives due to maternal antibiotics. In the absence of diagnostic confirmation, treatment is initiated upon suspicion of sepsis with broad spectrum antibiotics. Unfortunately, this strategy often misses the target and is associated with side effects, including damage to developing microbiomes. It is therefore critical to advance innovative diagnostic approaches which do not rely on culturing in order to facilitate accurate diagnosis and timely transition to evidence-based treatments. To address this unmet need, HelixBind developed RaPID/neo, a fully automated, sample-to-answer test for identifying BSIs directly from newborn blood within ~3 hours, without cultures. The test incorporates a broad test menu of 18 bacterial and fungal pathogens that make up the vast majority of neonatal sepsis cases. RaPID/neo is implemented on the RaPID (Resistance and Pathogen IDentification) platform, incorporating single-use test cassettes and a bench top Analyzer. RaPID/neo provides single CFUs/ml sensitivity across its test menu and is not confounded by polymicrobial infections nor prior antimicrobial treatment. In a preliminary clinical assessment, RaPID/neo demonstrated >92% sensitivity and 99% specificity across the assay. In this proposed Direct-to-Phase II project, HelixBind will build on its preliminary data to further product development by addressing analytical challenges associated with developing a test targeting this vulnerable patient population. We will review our findings and proposed studies for regulatory clearance with the FDA during a Pre-Submission process with the agency. Leveraging agency feedback, we will design an in-hospital study aimed at challenging our clinical studies plan in preparation for the pivotal trials for FDA clearance. To succeed in this endeavor, we have assembled an accomplished team with expertise in assay development, instrumentation, consumables manufacturing, clinical microbiology, and infectious disease as well as a successful track record of commercializing IVD platforms and assays. Together, we will build upon our preliminary work to complete product development, finalize a regulatory pathway, and challenge the system with an in-hospital study. Upon completion of this project, we will be well placed to initiate formal Analytical and Clinical studies for FDA clearance of RaPID/neo.

项目概要新生儿败血症是一种危及生命的疾病，在美国每 1,000 名活产儿中就有 2 名由新生儿败血症引起。侵袭性血流感染（BSI）发生在出生时或出生后不久，该疾病的初始临床表现通常是非特异性的、多变的，有时是微妙的，并且通常是早期压力的征兆。诊断后进行适当的抗菌干预是结果选择的关键预测因素。适当的抗菌药物受到当前检测和识别 BSI 的诊断过程的限制所有这些都依赖于原代血培养，速度很慢，通常需要数天才能得出结果，并且容易发生。由于母体抗生素导致的假阴性。在没有诊断确认的情况下，应根据情况开始治疗。不幸的是，这种策略常常达不到目标而被怀疑使用广谱抗生素。与副作用有关，包括对发育中的微生物组的损害，因此，推进这一点至关重要。不依赖培养的创新诊断方法，以促进准确诊断和及时过渡到循证治疗。为了解决这一未满足的需求，HelixBind 开发了 RaPID/neo，这是一种全自动、从样本到答案的测试，用于 BSI 可在约 3 小时内直接识别新生儿血液，无需培养。该测试包含广泛的测试。 18 种细菌和真菌病原体构成了绝大多数新生儿败血症病例。在 RaPID（耐药性和病原体识别）平台上实施，包含一次性测试盒和台式分析仪 RaPID/neo 在其测试菜单中提供单一 CFU/ml 灵敏度。在初步临床中，不会因多种微生物感染或先前的抗菌治疗而混淆。评估中，RaPID/neo 在整个检测中表现出 >92% 的灵敏度和 99% 的特异性。在这个拟议的直接进入第二阶段项目中，HelixBind 将以其初步数据为基础进一步开发产品通过解决与开发针对这一弱势群体的测试相关的分析挑战来进行开发我们将审查我们的发现和拟议的研究，以获得 FDA 的监管许可。在与机构的预提交过程中，我们将根据机构的反馈设计一个院内项目。研究旨在挑战我们的临床研究计划，为 FDA 批准的关键试验做准备。为了在这一努力中取得成功，我们组建了一支在检测开发方面拥有专业知识的优秀团队，仪器仪表、耗材制造、临床微生物学、传染病以及我们将共同努力，在 IVD 平台和检测商业化方面取得成功。完成产品开发、最终确定监管路径并对系统提出挑战的前期工作完成该项目后，我们就可以开始正式的分析。 FDA 批准 RaPID/neo 的临床研究。