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管制的药物市场。 美国近四分之三的致命药物过量是由美国各州和各州负责的。同时增加 芬太尼使用患者丁丙诺啡启动和维持治疗的挑战，包括 据报道，在标准剂量下，突然戒断和戒断和渴望控制不足。 丁丙诺啡的研究和临床方案是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给药方案。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更高的丁丙诺啡日剂量（24 mg） 在有芬太尼使用史的人群中耐受性良好，安全，更好地控制渴望，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 标准剂量，以评估使用芬太尼的人群的治疗结果。阿片类药物使用障碍（OUD） 与丁丙诺啡相比，死亡率降低了50%，并带来了其他个人健康和社会福利。返回 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% 治疗开始后3个月内。此外，据估计，40%的药物治疗患者 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 或者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影响为此，我们将首先进行定量和 定性混合方法研究（UG 3），以评价处方的每日剂量与 丁丙诺啡与非致死性和致死性药物过量的发生率，并确定最佳高剂量丁丙诺啡 维持治疗剂量用于后续RTC。在成功完成UG 3后，我们将 在250例有非处方芬太尼使用史的患者中进行RCT（UH 3），以比较 标准与高剂量维持丁丙诺啡方案。将通过调查积极跟踪参与者 和UDS评估在诊所预约1，3和6个月。被动监视将持续到 研究期旨在评价1个月时丁丙诺啡、非致死性和致死性过量的治疗保留，6 月和12个月的时间间隔，使用全州范围内的PINK、ME、EMS和艾德的管理数据库链接 数据集。本研究将提供芬太尼患者最佳丁丙诺啡给药疗效的新数据 用于指导OUD临床治疗的最佳实践。