Safety and Efficacy of High Dose Buprenorphine Induction in Fentanyl Positive Emergency Department Patients
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 2
- 主要终点
- The proportion of participants engaged in comprehensive addiction treatment at 7-days post-ED induction
研究概览
简要总结
This project, involving two distinct clinical trials, tests whether induction to a higher than currently recommended buprenorphine (BUP) induction dose is safe and can improve the proportion of patients who engage in comprehensive addiction services within 7-day of induction.
Trial 1 is a head-to-head comparison of the safety, tolerability and feasibility of high dose BUP induction (32 mg). The study involves two cohorts, (1) a 12mg cohort (standard) to determine baseline data and (2) a 32 mg (high dose) cohort. If the 32mg is intolerable, a 24 mg dose may be evaluated. Trial 2 is a small pilot multicenter randomized, double blinded, clinical trial in 80 participants (randomized 1:1) that will provide preliminary information on efficacy with the primary outcome being engagement in comprehensive addiction treatment 7-days post BUP induction. In collaboration with National Institute on Drug Abuse (NIDA), the research team have determined that there must be a minimum increase in engagement in comprehensive addiction treatment of 15% at 7-days in the high dose induction group to justify a larger future clinical trial.
详细描述
The design of Trial 1 and Trial 2 will be described separately. Trial 1 is a prospective test of the safety and tolerability of 32 mg of BUP as an induction dose (split dosing over 30-60 minutes with 4 hours of post-induction monitoring) with the recommended BUP induction dose (12mg, also split over 60 minutes). Dosing for the 12 mg cohort is planned to be 8 mg at t=0 and 4 mg at 30-60 min. The dosing for the 32 mg cohort is planned to be 16 mg at t=0 and 16 mg at 30-60 min.
The frequency of unacceptable dose limiting toxicities is set at >10%. The study will therefore compare two cohorts of 10 participants, with the potential for 5 extra participants per cohort if 1 dose limiting toxicity is observed in the first 10 subjects in a cohort.
If there are two dose limiting toxicities (DLTs) in the 32mg cohort, that cohort will no longer recruit. A new, 24 mg high dose cohort will be formed. If the 24 mg cohort has 2 DLTs in either 1st 10 patients or when expanded to n=15, it will be concluded that no safe/tolerable high induction dose has been identified and trial 2 will not occur.
If the 12 mg (control) cohort has 2 DLTs, at n=15 the Data and Safety Monitoring Board (DSMB) will be consulted about enlarging the cohort size or other modifications.
Any participants in the 12 mg cohort who choose not to take their full assigned dose will be replaced to ensure the full cohort size. No more than 20% of participants in either 24 mg or 32 mg cohorts who choose not to take their full assigned dose can be replaced.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
In trial 1 neither the investigator nor the participant will be blinded to group assignment. In Trial 2, participants, Investigators and site personnel with the exception of the investigational drug pharmacist will be blinded to group assignment.
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
- •Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study
- •Treated in the ED during screening hours
- •Meet DSM-5 diagnostic criteria for moderate to severe OUD
- •Clinical Opioid Withdrawal Score (COWS) score ≥ 8
- •Urine toxicology positive for fentanyl
- •Able to speak English or Spanish sufficiently to understand study procedures
排除标准
- •UDS positive for methadone.
- •Be pregnant determined by urine human chorionic gonadotropin (uHCG) testing
- •Have an unstable medical or psychiatric condition including suicidality requiring hospitalization
- •Require ongoing opioids for pain management
- •Be enrolled in formal addition treatment including by court order anytime within the last 30 days. Patients enrolled in formal addiction treatment not receiving Medications for Opioid Use Disorder (MOUD) are eligible
- •Be a prisoner or in custody at the time of the index visit
- •Have any pending legal status or pending legal action that could prohibit full participation in or compliance with study procedures.
- •Unable to provide one additional point of contact other than themselves
- •Unwilling to follow study procedures
- •Have prior enrollment in the current study
- •Have a known allergy or hypersensitivity to BUP
- •Have been engaged in formal addiction treatment in the 30-days prior to the ED visit (this does not include addiction treatment or residential programs where MOUD is not given (e.g. behavioral counseling, abstinence programs, NA)
- •Have received naloxone in the 60-minutes prior to the anticipated first transmucosal (TM) BUP administration
- •Is undergoing concurrent treatment with another investigational agent or enrolment in another clinical study
研究组 & 干预措施
Buprenorphine High Dose
The experimental arm tests the safety and tolerability of 32mg of BUP split as 16mg at time=0 and 16mg at time=30-60 min as an induction dose.
干预措施: High Dose Buprenorphine (Drug)
Buprenorphine Standard Dose
The standard arm will receive an induction dose of 12mg of buprenorphine (BUP) split as 8mg at time=0 and 4mg at time=30-60 min.
干预措施: Standard Buprenorphine Dose (Drug)
结局指标
主要结局
The proportion of participants engaged in comprehensive addiction treatment at 7-days post-ED induction
时间窗: 7 days post-ED visit
The proportion of participants engaged in comprehensive addiction treatment at 7 days post-ED induction as verified by participant and the addiction treatment program.
次要结局
- Percentage of days with opioid use (Trial 2)(30 days post-ED)
- Daily assessment of opioid use (Trial 1)(Days 1-7 after enrollment)
- Proportion of participants with a Pasero Opioid-induced Sedation Scale (POSS) score of 3 or higher(at 240 minutes)
- Proportion of participants with a Mini Mental Status Exam (MMSE) score indicating severe cognitive impairment(at 240 minutes)
- Patient Satisfaction Survey(ED enrollment visit at 240 minutes)
- Percentage of days with opioid use (Trial 1)(7 days post-ED)
- Change in number of times opioids used (Trial 1)(induction through 7 days)
- Proportion of participants with persistent nausea/vomiting during induction(at 240 minutes)
- Proportion of participants with precipitated or worsening withdrawal(up to 240 minutes)
- Percentage of days with opioid abstinence (Trial 1)(at day 7)
- Change in number of times opioids used (Trial 2)(Baseline and follow-up assessment day 30)
- Change in number of times opioids used (Trial 2)(Baseline and follow-up assessment day 7)
研究者
Ethan Cowan, MD
Professor
Rutgers, The State University of New Jersey