Develoment and clinical evaluation of a POC theranostic assay to inform therapy choice in Acute Respiratory Distress Syndrome

POC 治疗诊断测定的开发和临床评估，为急性呼吸窘迫综合征的治疗选择提供信息

• 批准号: 104639
• 金额: $ 148.68万
• 依托单位: RANDOX LABORATORIES LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=104639
• 关键词: Develoment; clinical; evaluation; POC; theranostic

"Acute Respiratory Distress Syndrome (ARDS) is a life threatening condition in critically ill patients, caused by infection or injury. Infection and injury induce inflammation in the lungs, causing the lungs to fill up with fluid thus preventing the normal movement of oxygen from the lungs to the blood, for distribution to the rest of the body. ARDS often progresses to further injury to other organs in the body, and is associated with high rates of mortality or long term disability in survivors.The incidence of ARDS is estimated to be 40,000 patients annually in the UK, 200,000 in the US and 3 million globally. Mortality rates range between 30-45%, depending on initial severity at diagnosis. There is no effective drug treatment for the condition despite numerous clinical trials to evaluate possible candidates. However, new evidence suggests that previously tried and discounted drugs may benefit certain patient sub-groups. Medical experts within our project consortium have found that ARDS patients with very high levels of certain markers of inflammation are more likely to respond to several therapies. Several biomarkers (substances we can measure in blood) have been identified to allow identification of these hyper-inflamed patients. This is the essence of stratified medicine, where a diagnostic test can inform individual therapy decisions, also known as theranostics. To allow rapid identification of the hyper-inflamed patient with ARDS, and hence guide the most effective therapy at the point of admission to Intensive Care Units, a near-patient theranostic test is required.Working with our clinical and academic partners, Randox have developed a test to identify hyper-inflamed ARDS patients and confirmed this works by testing over 120 blood samples. This project proposal will further develop this biomarker test to allow rapid near-patient analysis, using our new point of care (POC) diagnostic analyser. Once ready, our clinical / academic partners at Queen's University Belfast will co-ordinate a multi-centre clinical evaluation across Intensive Care Units in the UK to show that the test can be used at point of care to accurately stratify patients into hyper-inflamed and hypo-inflamed phenotypes (sub-groups). This will inform therapy decisions.The project thus aims to develop a theranostic ARDS test and prove that it is effective in identifying those critically ill patients that are more likely to respond to a tailored therapy."

急性呼吸窘迫综合征（ARDS）是由感染或损伤引起的危重病人的一种危及生命的疾病。感染和损伤会引起肺部的炎症，导致肺部充满液体，从而阻止氧气从肺部正常进入血液，并分配到身体的其他部位。ARDS通常发展为对身体其他器官的进一步损伤，并与幸存者的高死亡率或长期残疾有关。据估计，英国每年有4万例ARDS患者，美国20万例，全球300万例。死亡率在30-45%之间，取决于诊断时的初始严重程度。尽管进行了大量的临床试验来评估可能的候选药物，但目前还没有有效的药物治疗方法。然而，新的证据表明，以前试用过和打折的药物可能对某些患者亚组有益。我们项目联盟的医学专家发现，某些炎症标志物水平非常高的ARDS患者更有可能对几种治疗产生反应。已经确定了几种生物标志物（我们可以在血液中测量的物质）来识别这些高度炎症的患者。这是分层医学的本质，在分层医学中，诊断测试可以为个体治疗决策提供信息，也称为治疗学。为了快速识别严重炎症的急性呼吸窘迫综合征患者，从而在重症监护病房入院时指导最有效的治疗，需要进行近患者治疗试验。Randox与我们的临床和学术合作伙伴合作，开发了一种检测方法来识别高度炎症的ARDS患者，并通过测试120多个血液样本证实了这种方法的有效性。该项目提案将进一步开发这种生物标志物测试，使用我们新的护理点（POC）诊断分析仪，实现快速的近患者分析。一旦准备好，我们在贝尔法斯特女王大学的临床/学术合作伙伴将协调英国重症监护病房的多中心临床评估，以表明该测试可以在护理点使用，准确地将患者分为高度炎症和低炎症表型（亚组）。这将为治疗决策提供信息。因此，该项目旨在开发一种治疗性ARDS测试，并证明它在识别那些更有可能对量身定制的治疗有反应的危重患者方面是有效的。”