Safety and Efficacy of High Dose Buprenorphine Induction in Fentanyl Positive Emergency Department Patients

摘要 UG3/UH3是基于需要确定丁丙诺啡(BUP)的最佳诱导策略 未经治疗的阿片使用障碍患者(OUD)。先前的BUP诱导研究和指南，包括 来自物质滥用和精神健康服务管理局，美国成瘾协会 医学和美国急诊医学院在治疗BUP剂量方面有所不同 归纳法。此外，现行准则是在非法药物中芬太尼扩散之前制定的。 供给。最近，有报道指出，使用芬太尼的患者在使用芬太尼时会有更多的困难。 有更多恶化/催促戒断事件的BUP诱导。这些担忧导致了核扩散。 各种BUP诱导策略，从低和慢的“微量剂量”到快速的“超治疗”BUP 给药。该提案旨在确定标准丁丙诺啡诱导是否会导致更多 芬太尼阳性使用者的恶化/催促戒断事件比其他阿片类药物依赖患者和 检查单次大剂量BUP诱导的安全性、耐受性、可接受性和临床效果 急诊科(ED)未经治疗的患者的策略。 UG3的具体目标。目标1a。首先，我们将开发和手动升级大剂量BUP诱导 可以在ED中以高保真方式提供的协议。1B.然后我们将评估其安全性和耐受性。 芬太尼阳性ED患者3个10人队列(16 mg、24 mg、32 mg)BUP初始剂量的增加 未经治疗的OUD符合ED启动BUP的标准。1C。我们将收集以患者为中心的数据和 手术结果包括患者满意度、抢救剂量和辅助药物的需求。目标 2.在具有良好边缘的四个站点执行高BUP诱导与标准BUP诱导的多中心RCT试点 BUP启动计划，以证明可行性并验证患者满意度。2A。比较最优最高 80例芬太尼阳性患者的剂量诱导策略从目标1到“标准”ED诱导策略 符合勃起功能障碍标准的勃起功能障碍患者随机分为1：1.2B。评估主要综合结果 在每个研究组中都有加速/恶化的戒断症状。2C。比较二次以患者为中心和 每个研究分支的操作结果。 UH3的具体目标。目标1a。在四个UG3站点执行的多中心RCT中，比较高与 标准剂量BUP诱导1：1随机对照研究恶化/沉淀的主要综合结局 708例患者停药。目标2a。比较大剂量BUP诱导与标准BUP诱导 BUP诱导后7天参与综合成瘾治疗的临床疗效结果。 2B。比较研究组之间以患者为中心的结果和实施结果。

Summary This UG3/UH3 is based on the need to identify optimal induction strategies for buprenorphine (BUP) in patients’ with untreated opioid use disorder (OUD). Prior BUP induction studies and guidelines including those from the Substance Abuse and Mental Health Services Administration, the American Society of Addiction Medicine and the American College of Emergency Medicine differ with regard to BUP dosing for treatment induction. Furthermore, existing guidelines were developed before the proliferation of fentanyl in the illicit drug supply. Recently, reports have raised concerns that patients with OUD using fentanyl have more difficulty with BUP induction with more worsening/precipitated withdrawal events. These concerns have led to a proliferation of BUP induction strategies that range from low–and-slow “micro-dosing” to rapid “supra-therapeutic” BUP dosing. This proposal aims to determine whether standard buprenorphine induction results in more worsening/precipitated withdrawal events in fentanyls-positive users than other opioid-dependent patients and to examine the safety, tolerability, acceptability and clinical effectiveness of a single high dose BUP induction strategy in Emergency Department (ED) patients with untreated OUD. UG3 specific aims. Aim 1a. First we will develop and manualized escalating high dose BUP induction protocols that can be delivered with high fidelity in the ED. 1b. Then we will evaluate the safety and tolerability of escalating initial BUP dose in three 10-person cohorts (16mg, 24mg, 32mg) of fentanyl positive ED patients with untreated OUD meeting criteria for ED initiated BUP. 1c. We will collect data on patient centered and operational outcomes including patient satisfaction, need for rescue BUP doses and ancillary medications. Aim 2. Perform a pilot multicenter RCT of high versus standard BUP induction at four sites with well-established ED BUP initiation programs to prove feasibility and validate patient satisfaction. 2a. Compare the optimal high dose induction strategy from Aim 1 to a “standard” ED induction strategy in 80 (20 per site) fentanyl positive ED patients meeting criteria for ED initiated BUP randomized 1:1. 2b. Assess the primary composite outcome of precipitated/worsening withdrawal in each study arm. 2c. Compare secondary patient centered and operational outcomes in each study arm. UH3 specific aims. Aim 1a. In a multicenter RCT performed at the four UG3 sites, compare high versus standard dose BUP induction randomized 1:1 on the primary composite outcome of worsening/precipitated withdrawal in 708 patients. Aim 2a. Compare high-dose BUP induction to standard BUP induction on the clinical efficacy outcome of engagement in comprehensive addiction treatment at 7-days post BUP induction. 2b. Compare patient centered and implementation outcomes between study arms.