Identifying optimal buprenorphine dosing for OUD treatment and prevention of overdose

确定 OUD 治疗的最佳丁丙诺啡剂量和预防过量

• 批准号: 10524852
• 负责人: Francesca Beaudoin
• 金额: $ 42.5万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10524852
• 关键词: Address; Adherence; Anecdotes; Appointment; Award; Buprenorphine; Case Study; Chronic; Clinic; Clinical; Clinical Protocols; Clinical Treatment; Clinical Trials; Contracts; Data; Data Collection; Data Set; Dose; Electronic Health Record; Enrollment; Fentanyl; Floods; Future; Guidelines; Health; Individual; Interview; Link; Maintenance; Measures; Medicine; Methods; Motivation; Outpatients; Overdose; Participant; Patients; Persons; Pharmaceutical Preparations; Pharmacodynamics; Phase; Population; Procedures; Protocols documentation; Provider; Public Health; Randomized Controlled Trials; Recording of previous events; Reporting; Research; Risk; Safety; Specialist; Standardization; Surveys; Symptoms; Testing; Training; Treatment outcome; United States; Update; Withdrawal; Work; addiction; administrative database; analog; base; buprenorphine treatment; clinical practice; cohort; comparative effectiveness; comparative efficacy; craving; dosage; drug market; effectiveness evaluation; efficacy evaluation; evidence base; follow-up; heroin use; high risk; human subject protection; illicit opioid; improved; mortality; novel; opioid use; opioid use disorder; overdose death; overdose prevention; overdose risk; prescription opioid; primary endpoint; prospective test; recruit; secondary endpoint; social; substance use; synthetic opioid; treatment effect

PROJECT ABSTRACT Synthetic opioids including fentanyl and its analogs have flooded the unregulated drug market in the United States and are responsible for nearly three quarters of the nation’s fatal drug overdoses. Concurrently increased challenges of buprenorphine initiation and maintenance treatment in patients with fentanyl use including risk of precipitated withdrawal and inadequate control of withdrawal and cravings at standard doses are being reported. Buprenorphine research and clinical protocols were based on heroin using populations. There are no updated standardized buprenorphine maintenance dosing protocols for patients using fentanyl. Data from our own clinical practice and other buprenorphine maintenance providers suggests higher daily doses of buprenorphine (24 mg) are well-tolerated, safe, and better control cravings in populations with a history of fentanyl use, yet this strategy has neither been tested prospectively or retrospectively in a randomized controlled trial (RCT) nor compared to standard dosing to assess treatment outcomes in populations using fentanyl. Treating opioid use disorder (OUD) with buprenorphine decreases mortality by 50% and confers other personal health and social benefits. Return to use rates for patients on buprenorphine treatment are high; a recent study reported rates greater than 50 % within 3 months of treatment initiation. Additionally, It has been estimated that 40% of patients on medications for opioid use (MOUD) continue non-prescribed opioid use during treatment, yet we lack understanding of how or why ongoing fentanyl use occurs during buprenorphine therapy, the effects of treatment outcomes, and the impact of buprenorphine dose on fentanyl use practices. For this reason, we will first conduct a quantitative and qualitative mixed method study (UG3) to evaluate if there is an association between daily dose of prescribed buprenorphine and occurrence of non-fatal and fatal overdose and determine the optimal high buprenorphine maintenance treatment dose to use in the subsequent RTC. After successful completion of the UG3, we will conduct a RCT (UH3) in 250 patients with a history of non-prescribed fentanyl use to compare efficacy of standard vs. high dose maintenance buprenorphine protocols. Participants will be actively followed via surveys and UDS assessments at clinic appointments for 1, 3 and 6 months. Passive surveillance will continue throughout the study period to evaluate treatment retention on buprenorphine, non-fatal and fatal overdose at 1 month, 6 months, and 12 month intervals using administrative database linking of state-wide PDMP, ME, EMS, and ED datasets. This study will provide novel data on optimal buprenorphine dosing efficacy in patients with fentanyl use to inform best practices for clinical treatment of OUD.

项目摘要 包括芬太尼及其类似物在内的合成阿片类药物充斥着美国不受监管的药物市场 全国近四分之三的致命吸毒过量事件均由各州负责。 使用芬太尼的患者丁丙诺啡初始治疗和维持治疗面临的挑战包括风险 据报道，在标准剂量下会出现突然戒断以及对戒断和渴望的控制不充分。 丁丙诺啡研究和临床方案基于海洛因使用人群，没有更新。 使用芬太尼的患者的标准化丁丙诺啡维持剂量方案来自我们自己的临床数据。 实践和其他丁丙诺啡维持提供者建议较高的丁丙诺啡每日剂量（24 毫克） 对于有芬太尼使用史的人群来说，耐受性良好、安全且能更好地控制对芬太尼的渴望，但这种策略 既没有在随机对照试验（RCT）中进行前瞻性或回顾性测试，也没有与 评估使用芬太尼的人群的治疗结果的标准剂量治疗阿片类药物使用障碍（OUD）。 丁丙诺啡可使死亡率降低 50%，并带来其他个人健康和社会效益。 接受丁丙诺啡治疗的患者的使用率很高；最近的一项研究报告使用率超过 50% 此外，据估计，40% 的患者在开始治疗后 3 个月内正在接受药物治疗。 对于阿片类药物使用 (MOUD) 在治疗期间继续使用非处方阿片类药物，但我们缺乏了解如何 或为什么在丁丙诺啡治疗期间持续使用芬太尼、治疗结果的影响以及 丁丙诺啡剂量对芬太尼使用实践的影响为此，我们首先进行定量和分析。 定性混合方法研究 (UG3)，用于评估每日处方剂量之间是否存在关联 丁丙诺啡与非致命和致命过量的发生情况并确定最佳高丁丙诺啡 成功完成 UG3 后，我们将在后续 RTC 中使用维持治疗剂量。 对 250 名有非处方芬太尼使用史的患者进行随机对照试验 (UH3)，以比较以下药物的疗效 标准与高剂量维持丁丙诺啡方案将通过调查积极跟踪。 诊所预约时的 UDS 评估将持续 1、3 和 6 个月。 评估丁丙诺啡治疗保留情况的研究期，1个月时的非致命性和致命性过量用药，6 个月和 12 个月的间隔，使用全州 PDMP、ME、EMS 和 ED 的管理数据库链接 这项研究将提供有关芬太尼患者丁丙诺啡剂量疗效的最佳新数据。 用于为 OUD 临床治疗的最佳实践提供信息。