Rapid Outpatient Low-dose Initiation of Buprenorphine for Individuals With OUD Using Fentanyl
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Initiation of buprenorphine maintenance without precipitated withdrawal
研究概览
简要总结
The goal of this clinical trial is to learn if buprenorphine can be started for opioid use disorder with fentanyl use without requiring or precipitating opioid withdrawal. To be eligible, participants must have moderate or severe opioid use disorder and must have fentanyl detected on a urine drug test.
Participants will be admitted to a monitored research unit for the trial. They will be randomized to start buprenorphine with either standard initiation or with a new approach called rapid outpatient low-dose initiation (ROLDI).
For standard initiation, participants will be instructed to arrive to the unit with at least 8 hours since last fentanyl use. Once they have at least moderately severe opioid withdrawal (Clinical Opiate Withdrawal Scale [COWS] 11 or higher), participants will receive 2 mg, 2 mg, 4 mg, and then 8 mg sublingual buprenorphine, with doses every 2 hours. They will then continue 8 mg twice daily (or up to three times daily). This is the current standard of care.
For ROLDI, participants will not be required to have a period abstinence, they will have no or minimal withdrawal (COWS 4 or less) when starting buprenorphine, and participants will take 0.5, 0.5, 0.5, 0.5, 2, 16 mg with doses scheduled every 2 hours. They will then continue 8mg twice daily (or up to three times daily).
The main aim of this clinical trial is to assess whether ROLDI is safe, feasible, acceptable to patients, and worthwhile to study in a larger trial. The secondary aim is to describe fentanyl and norfentanyl pharmacokinetics (that is to say, fentanyl and norfentanyl concentration in blood and urine) during early abstinence to understand why some people using fentanyl develop precipitated withdrawal with standard initiation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 18 or older
- •Male, female, transgender, or non-binary
- •DSM-5 criteria for opioid use disorder, moderate to severe
- •Fentanyl positive on urine drug test
- •Able to provide written informed consent in English prior to any study-related procedure
排除标准
- •Pregnancy or actively lactating
- •Previously documented hypersensitivity or allergy to buprenorphine or naloxone
- •DSM-5 criteria for substance use disorder other than opioid use disorder (e.g., cannabis, cocaine, alcohol)
- •Current benzodiazepine use
- •Urine drug testing at screening positive for buprenorphine and/or methadone
- •AST and/or ALT >3x upper limit of normal or total bilirubin >1.5x upper limit of normal
- •eGFR <30 mL/min
- •Use of CYP3A4-metabolized agents such as azole antifungals, macrolides, and protease inhibitors
- •High risk of severe medetomidine withdrawal based on drug urine testing for medetomidine, prior withdrawal syndrome requiring intensive care unit admission, and/or patient-reported severe nausea/vomiting during early withdrawal, at the discretion of the study physicians.
- •Significant medical symptoms (e.g. severe respiratory insufficiency), psychiatric symptoms, or dementia that, in the opinion of the investigators, would preclude compliance with the protocol, cooperation in the study, obtaining informed consent, or ability to safely participate in the study
- •Pending legal action that could prohibit participation and/or compliance in study procedures
研究组 & 干预措施
Rapid outpatient low-dose initiation
Participants randomized to low-dose initiation will be instructed to arrive to the research unit without withdrawal. Participants with COWS <4 will be admitted to the research unit to begin induction. They will be administered 0.5, 0.5, 1, 1, 1, 4, and then 8 mg as sublingual buprenorphine films with doses scheduled every 2 hours. They will then continue 8mg twice daily (or up to three times daily) as maintenance treatment.
干预措施: Buprenorphine (Drug)
Standard initiation
Participants randomized to standard induction will be instructed to arrive to the research unit with mild withdrawal and to have abstained from opioids for at least 8 hours, per ASAM Guidelines. Participants with COWS 4 or higher on initial assessment will be admitted to the research unit to begin induction.
Standard initiation will follow guidelines from the 2020 Focused Update of the ASAM National Practice Guidelines. Once participants have had at least 8 hours of abstinence and have reached COWS 11 or greater, they will be given 2 mg sublingual buprenorphine, followed 2 hours later by 2 mg, followed 2 hours later by 4 mg, followed 2 hours later by 8 mg. They will then continue 8 mg twice (or up to three times) daily as maintenance treatment.
干预措施: Buprenorphine (Drug)
结局指标
主要结局
Initiation of buprenorphine maintenance without precipitated withdrawal
时间窗: 10 hours
The proportion of subjects who complete buprenorphine initiation without precipitated withdrawal. Completing buprenorphine initiation is defined as reaching 8mg or more total daily dose of sublingual buprenorphine without termination of buprenorphine initiation for any reason. Precipitated withdrawal is defined as an increase in COWS of 6 or more (compared to the COWS immediately preceding the most recent dose of buprenorphine) within 2 hours of the most recent dose of sublingual buprenorphine.
次要结局
未报告次要终点
研究者
Kyle Kampman
Professor of Psychiatry
University of Pennsylvania