Sentanyl II: A Multi-State Analysis of Fentanyl/Analogs, Naloxone, and Clinical Features of Non-Fatal Opioid Overdose

Sentanyl II：芬太尼/类似物、纳洛酮的多状态分析以及非致命阿片类药物过量的临床特征

• 批准号: 10904337
• 负责人: KAVITA M BABU
• 金额: $ 11.93万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10904337
• 关键词: Accident and Emergency department; Address; Administrative Supplement; Autopsy; Biological Assay; Blood; Blood specimen; Characteristics; Clinical; Clinical Data; Clinical Trials; Drug Kinetics; Education; Emergency Department patient; Fentanyl; Forensic Sciences; Grant; Hour; Human; Human Volunteers; Injections; Investigation; Investigational New Drug Application; Knowledge; Laboratories; Massachusetts; Mediating; Medical center; Naloxone; Opioid; Overdose; Parents; Participant; Patients; Persons; Pharmaceutical Preparations; Population; Predictive Value; Probability; Research; Sampling; Specificity; Specimen; Testing; Therapeutic Uses; U-Series Cooperative Agreements; United States National Institutes of Health; Universities; Urine; Xylazine; analog; comparative; exposed human population; illicit opioid; insight; interest; opioid overdose; parent project; performance tests; point of care; recruit; response; test strip; therapy development

Abstract In response to PA-20-272 Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional), we are requesting a supplement to parent cooperative agreement UG3DA056892 (Sentanyl II: A Multi-State Analysis of Fentanyl/Analogs, Naloxone, and Clinical Features of Non-Fatal Opioid Overdose). Although this notice cannot be used for this supplement request, Notice Special nevertheless Aim of Interest (NOSI): Xylazine: Understanding its Use and the Consequences (NOT-DA-24-009), encourages research on xylazine, and xylazine is the topic of the supplement request. 2 of the parent project, Sentanyl II (UG3DA056892), which is in progress, involves obtaining demographic and clinical data and blood samples from University of Massachusetts Medical Center Emergency Department (ED) opioid overdose patients. Blood samples undergo extensive assessment for opioids and other substances by the Center for Forensic Science Research and Education (CFSRE). Highly relevant to the topic of this supplement request, xylazine has been detected in the blood of 10 of 26 (38.5%) Sentanyl II participants whose blood samples have been analyzed to date by CFSRE. Xylazine has been used as an intentional adulterant in illicit opioids since approximately 2000. It increasingly has been detected in the illicit opioid supply and the post-mortem specimens from people with fentanyl-associated overdoses. Little is known about the pharmacokinetics of xylazine among humans since xylazine has no approved therapeutic use in people. This absence of knowledge reduces our ability to understand the expected clinical course of those who used xylazine, as well as the development of treatments to mediate its effects. A human volunteer study to evaluate xylazine pharmacokinetics is not possible, given that an investigational new drug application for human use of xylazine is unlikely, and subjecting participants to the drug is hazardous. Sentanyl II provides a naturalistic and practical opportunity to study xylazine pharmacokinetics. Furthermore, it provides a means to examine current point-of-care urine tests for xylazine among recently exposed human participants. For Supplement Aim 1, we will recruit twelve UMass ED patients who (1) present after opioid overdose via injection use, and (2) whose initial blood sample obtained on arrival at the ED indicates a probable xylazine exposure, per the Randox Laboratories Evidence MultiSTAT xylazine assay. Participants will provide additional blood samples hourly for up to six hours. CFSRE will perform quantitative analyses of these samples to produce xylazine pharmacokinetic profiles of these participants. For Supplement Aim 2, we will evaluate the test performance characteristics (e.g., sensitivity, specificity, predictive value) of the ResponseTM Xylazine Test Strip), as compared to the comparative “gold standard” of CFSRE blood sample testing.

抽象的 响应 PA-20-272 对现有 NIH 拨款和合作协议的行政补充 （家长管理补充临床试验可选），我们要求家长合作协议的补充 UG3DA056892（Sentanyl II：芬太尼/类似物、纳洛酮和临床特征的多状态分析 非致命阿片类药物过量）虽然本通知不能用于此补充请求，但通知 特别的 尽管如此 目的 的 兴趣 (NOSI)：赛拉嗪：了解其用途和后果 (NOT-DA-24-009)， 鼓励对甲苯噻嗪的研究，而甲苯噻嗪是补充请求的主题。 正在进行的父项目 Sentanyl II (UG3DA056892) 的第 2 部分涉及获取 来自马萨诸塞大学紧急医疗中心的人口统计和临床数据以及血液样本 科室 (ED) 对阿片类药物过量患者的血液样本进行阿片类药物和其他药物的广泛评估。 法医科学研究和教育中心 (CFSRE) 的物质与主题高度相关。 在本补充请求中，26 名 Sentanyl II 参与者中的 10 名 (38.5%) 的血液中检测到了甲苯噻嗪 迄今为止，其血液样本已由 CFSRE 进行了分析。 自大约 2000 年以来，赛拉嗪一直被用作非法阿片类药物中的故意掺杂剂。 在非法阿片类药物供应和患有此类疾病的人的尸检样本中越来越多地发现了这种物质。 自那时起，人们对甲苯噻嗪在人类中的药代动力学知之甚少。 赛拉嗪尚未获得批准用于人类治疗用途。这种知识的缺乏降低了我们治疗的能力。 了解使用甲苯噻嗪的患者的预期临床病程，以及治疗方法的开发 鉴于此，不可能进行人体志愿者研究来评估甲苯噻嗪的药代动力学。 用于人类使用甲苯噻嗪的研究性新药申请不太可能，并且需要遵守 Sentanyl II 为研究甲苯噻嗪提供了一个自然且实用的机会。 此外，它还提供了一种检查当前甲苯噻嗪尿检的方法。 在最近暴露的人类中。 对于补充目标 1，我们将招募 12 名麻省大学急诊科患者，他们 (1) 在阿片类药物过量后通过 注射使用，以及 (2) 到达急诊室时获得的初始血液样本表明可能含有赛拉嗪 根据 Randox Laboratories Evidence MultiSTAT xylazine 测定，参与者将提供额外的暴露量。 CFSRE 每小时抽取一次血液样本，持续时间长达 6 小时。 对于补充目标 2，我们将评估这些参与者的甲苯噻嗪药代动力学特征。 ResponseTM Xylazine 测试的测试性能特征（例如灵敏度、特异性、预测值） Strip），与 CFSRE 血液样本测试的比较“金标准”进行比较。