A rapid microfluidic diagnostic assay for the measurement of Direct Oral Anticoagulants from patient whole blood

一种快速微流体诊断测定法，用于测量患者全血中的直接口服抗凝剂

• 批准号: 10615908
• 负责人: Adam Cuker
• 金额: $ 41.31万
• 依托单位: FLOBIO, LLC
• 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 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10615908
• 关键词: Adult; Anticoagulants; Anticoagulation; Antithrombin III; Area; Arrhythmia; Automation; Biological Assay; Blinded; Blood; Blood Circulation; Blood Platelets; Blood Vessels; Blood coagulation; Blood specimen; Capital; Caring; Classification; Clinic; Clinical; Clinical Data; Clinical Research; Coagulation Process; Collagen Type I; Computer software; Critical Care; Data; Data Set; Decision Making; Detection; Development; Devices; Diagnostic; Disease; Emergency Care; Event; FDA approved; Fibrin; Goals; Health Personnel; Hemophilia A; Hemorrhage; Human; Image; In Vitro; Investments; Joints; Knowledge; Laboratories; Length; Manuals; Marketing; Measurement; Measures; Medicine; Microfluidic Microchips; Microfluidics; Monitor; Operative Surgical Procedures; Oral; Outcome; Outcome Assessment; Patients; Pennsylvania; Performance; Pharmaceutical Preparations; Phase; Physicians; Physiological; Process; Production; Proteins; Reagent; Reporter; Reproducibility; Risk; Running; Safety; Sampling; Sensitivity and Specificity; Signal Transduction; Site; Specificity; Stroke; System; Testing; Thrombin; Thromboplastin; Thrombosis; Time; Trauma; Universities; Variant; Warfarin; Whole Blood; Work; analytical method; diagnostic assay; evidence base; hemodynamics; improved; in vivo; in-vitro diagnostics; inhibitor; innovation; instrument; meetings; novel strategies; patient population; point-of-care diagnostics; product development; programs

Abstract: Direct oral anticoagulants (DOACs) are becoming the preferred approach to managing anticoagulation, particularly in thrombolytic disorders. DOAC use is anticipated to reach $30B globally in the next five years, overtaking other anticoagulants such as warfarin. While highly effective, DOACs can elevate bleeding risks, and complicate emergency care, which may include the use of expensive DOAC reversal agents. As current diagnostics fail to adequately identify problems caused by DOACs, there exists growing safety concerns for this class of drugs that are reinforced by the Joint Commission’s call for laboratory test monitoring, and evidence- based approaches for safe DOAC, and reversal agent use. Whether treating a stroke/VTE/PE patient, heart arrhythmia patient, or trauma/urgent surgery patient, the real-time determination of a patient’s state of anticoagulation, including DOAC type (factor Xa inhibitor vs. direct thrombin inhibitor) is critical for rapid care decisions to avoid adverse bleeding. A significant limitation of core laboratory detection of DOACs is the length of time to results, which can exceed more than the typical 20-minute decision making window. FloBio is developing the first DOAC in vitro diagnostic product to provide physicians with rapid knowledge of anticoagulation state in emergency care settings. With our analyzer/imaging station, and disposable DOAC assay cartridge/microfluidic device, our novel approach combines hemodynamic flow, and discrete clot activation, to mimic physiological blood clotting. In less than 10 minutes, a healthcare provider will know a patient’s relative DOAC concentration, and the DOAC classification. FloBio’s Phase I work has demonstrated a scalable, multiplex, disposable DOAC assay cartridge/microfluidic device that facilitates the natural blood clotting cascade in vitro, an instrument for measuring assay signals, analytic software to provide the end user with a simple outcomes assessment, and clinical data that validates the feasibility of the assay and device to detect DOAC class and level in human blood. FloBio’s innovation is a diagnostic assay that will be the first in the market to provide real-time data on fibrin and platelet accumulation on basal vascular and coagulation proteins, under flow, that recapitulates in vivo coagulation processes. In Phase II, FloBio will focus on validating the DOAC assay in a 100 subject clinical study at the University of Pennsylvania. This study will validate the capability of the assay to detect both class and DOAC level, within a clinical patient population. A second clinical study with DOAC spiked healthy adult blood will determine the device, assay and system range, sensitivity, specificity, variance, and consistency. Clinical assay data will be validated against the gold standard of detection, LCMS. Automation of critical assay functions will also be evaluated to reduce variation in the assay, and the feasibility of a fully integrated, automatable, disposable DOAC assay cartridge will be demonstrated in healthy human blood samples. The outcome of the work will be a fully vetted DOAC assay system that is ready for full development in Phase IIb.

摘要：直接口服抗凝药（DOAC）正在成为治疗糖尿病的首选方法。 抗凝治疗，尤其是溶栓疾病中 DOAC 的使用预计明年将达到 30B 美元。 五年后，DOAC 超越了华法林等其他抗凝药物，虽然非常有效，但它会增加出血。 风险，并使紧急护理变得复杂，其中可能包括使用昂贵的 DOAC 逆转剂。 诊断无法充分识别 DOAC 引起的问题，对此存在越来越多的安全担忧 联合委员会呼吁实验室测试监测和证据强化了这一类药物 基于安全 DOAC 和逆转剂使用的方法是否治疗中风/VTE/PE 患者、心脏。 心律失常患者，或创伤/紧急手术患者，实时确定患者的状态 抗凝治疗，包括 DOAC 型（Xa 因子抑制剂与直接凝血酶抑制剂）对于快速护理至关重要 避免不良出血的决定 DOAC 核心实验室检测的一个显着限制是长度。 获得结果的时间可能超过 FloBio 典型的 20 分钟决策窗口。 开发第一个 DOAC 体外诊断产品，为医生提供快速的知识 使用我们的分析仪/成像站和一次性 DOAC 检测来确定紧急护理环境中的抗凝状态。 盒/微流体装置，我们的新颖方法结合了血流动力学流动和离散凝块激活，以 模拟生理性血液凝固，不到 10 分钟，医疗保健提供者就会知道患者的相对 DOAC。 浓度和 DOAC 分类。 FloBio 的第一阶段工作展示了一种可扩展、多重、一次性 DOAC 检测盒/微流体 促进体外自然凝血级联的装置，用于测量分析信号的仪器， 分析软件为最终用户提供简单的结果评估以及验证的临床数据 FloBio 创新的检测方法和设备检测人体血液中 DOAC 类别和水平的可行性。 诊断分析将是市场上第一个提供纤维蛋白和血小板积累实时数据的诊断分析 在流动下对基础血管和凝血蛋白进行分析，重现体内凝血过程。 在第二阶段，FloBio 将重点在伦敦大学的 100 名受试者临床分析研究中验证 DOAC 宾夕法尼亚州。这项研究将验证该检测方法在一定时间内检测类别和 DOAC 水平的能力。 临床患者群体的第二项临床研究将确定添加了 DOAC 的健康成人血液。 设备、测定和系统范围、灵敏度、特异性、方差和一致性。 关键检测功能的自动化也将根据检测黄金标准进行验证。 评估减少测定中的变化，以及完全集成、自动化、一次性 DOAC 的可行性 检测盒将在健康的人体血液样本中进行验证，该工作的结果将是一个完整的结果。 经过审查的 DOAC 检测系统已准备好在 IIb 期进行全面开发。