Using the Transdermal Patch for Buprenorphine Induction during Pregnancy: A Pilot Randomized Controlled Trial

怀孕期间使用透皮贴剂诱导丁丙诺啡：一项随机对照试验

• 批准号: 10738154
• 负责人: Jeannie Chen Kelly
• 金额: $ 20.84万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10738154
• 关键词: Adherence; American College of Obstetricians and Gynecologists; Black Populations; Buprenorphine; Case Series; Clinic; Clinical; Consensus; Data; Discipline of obstetrics; Dose; Dropout; Drops; Eligibility Determination; Equity; Etiology; Exercise; Face; Failure; Feasibility Studies; Feedback; Fetal Growth Retardation; Goals; Health Personnel; Hospital Costs; Hour; Incidence; Individual; Infant; Intervention; Interview; Investigational Drugs; Maternal Mortality; Maternal-fetal medicine; Methods; Michigan; Morbidity - disease rate; Neonatal; Neonatal Abstinence Syndrome; New Drug Approvals; Opioid; Opioid agonist; Outcome; Outpatients; Pain management; Patient-Focused Outcomes; Patients; Persons; Pharmaceutical Preparations; Phase; Population; Postpartum Hemorrhage; Pregnancy; Pregnant Women; Premature Birth; Prenatal care; Prevalence; Procedures; Process; Protocols documentation; Publishing; Race; Randomized; Randomized, Controlled Trials; Recommendation; Relapse; Reporting; Research; Research Activity; Research Methodology; Rural Population; Severities; Site; Specialist; Structure; Testing; Time; Treatment Protocols; United States; Universities; Washington; Withdrawal; Withdrawal Symptom; arm; barrier to care; black patient; buprenorphine treatment; comparative efficacy; design; efficacy evaluation; experience; follow-up; high risk; implementation science; improved; improved outcome; intervention delivery; intraamniotic infection; maternal opioid use; member; mortality; mu opioid receptors; multi-site trial; neonatal outcome; obstetric outcomes; obstetrical complication; opioid misuse; opioid use; opioid use disorder; overdose risk; participant enrollment; pregnant; prenatal; prospective; racism; recruit; retention rate; rural patients; success; treatment adherence; trial comparing

PROJECT ABSTRACT The prevalence of opioid use disorder (OUD) during pregnancy is rising, increasing the incidence of severe maternal, neonatal, and obstetrical morbidity and mortality. Although maternal OUD can be effectively treated with buprenorphine, leading to improved adherence to prenatal care and reduced obstetrical complications, fewer than 1 in 5 patients receive medication treatment for maternal OUD. In large part, so few pregnant women receive buprenorphine because it can be challenging to initiate effectively. Initiation (termed buprenorphine induction) must begin while a patient is in moderate withdrawal. If induction begins too early, buprenorphine will displace the other opioid from the μ receptor, precipitating severe withdrawal. Maternal withdrawal, both precipitated and anticipated, is associated with high relapse rates, non-adherence and lower treatment retention rates. Unsurprisingly, induction is a known critical time point for dropout in OUD treatment. Multiple alternative protocols for buprenorphine induction have been reported, including successful methods that do not require an opioid-free period or moderate withdrawal symptoms by using microdoses of buprenorphine, such as via a transdermal patch, as a bridge induction method to full sublingual doses. However, buprenorphine induction protocols have never been studied in pregnancy to determine the most effective type. We propose a prospective, mixed-methods study at two OUD-specific prenatal clinics to evaluate the feasibility of conducting an randomized controlled trial (RCT) comparing buprenorphine transdermal bridge induction versus standard sublingual induction in pregnant patients with OUD. In Aim 1, we will qualitatively assess feasibility domains using semi- structured interviews with 20 patients using buprenorphine to treat maternal OUD, 10 clinical team members who treats them, and 5 research team members. We will present the RCT protocol to interviewees, and ask for feedback on consensus-based criteria of recruitment capability, assessment procedures, and acceptability. We will solutions, ask interviewees to conduct a “premortem” exercise to predict potential etiologies of RCT failure, brainstorm and adapt the RCT protocol accordingly. In Aim 2, we will quantitatively assess intervention and research methods feasibility (eg, percentage of recruitment/retention goals, success of masking, intervention fidelity) and preliminary efficacy to minimize withdrawal symptoms by conducting a pilot RCT of bridge versus standard buprenorphine induction to treat maternal OUD (n=20 per arm). Results will provide preliminary data to aid in design of large, multi-site trial powered to rigorously assess the efficacy of induction methods on important obstetric and neonatal outcomes. If this larger trial shows that the bridge buprenorphine induction protocol is effective in multiple populations, this treatment protocol could be widely disseminated to improve outcomes for patients with maternal OUD and their infants.

项目摘要 妊娠期间阿片类药物使用障碍（OUD）的患病率正在上升，增加了严重 孕产妇、新生儿和产科发病率和死亡率。虽然母亲的OUD可以有效治疗， 与丁丙诺啡，导致改善坚持产前护理和减少产科并发症， 少于五分之一的患者接受母亲OUD的药物治疗。在很大程度上，很少有孕妇 接受丁丙诺啡，因为它可以是具有挑战性的有效启动。开始（称为丁丙诺啡 诱导）必须在患者处于中度戒断时开始。如果诱导开始太早，丁丙诺啡将 取代μ受体中的另一种阿片类药物，导致严重戒断。母亲戒断，两者 加速和预期的，与高复发率、不依从性和较低的治疗保留相关 rates.不出所料，诱导是OUD治疗中脱落的已知关键时间点。多个备选 已经报道了丁丙诺啡诱导的方案，包括不需要药物诱导的成功方法。 无阿片类药物期或中度戒断症状，通过使用微剂量丁丙诺啡，如通过 透皮贴剂，作为一个桥梁诱导方法，以充分舌下剂量。然而，丁丙诺啡诱导 在怀孕期间从未研究过方案以确定最有效的类型。我们提出一个前瞻性的， 在两个OUD特定产前诊所进行的混合方法研究，以评估进行随机 比较丁丙诺啡经皮桥接诱导与标准舌下给药的对照试验（RCT） 妊娠期OUD患者的引产。在目标1中，我们将定性评估可行性域使用半- 对20名使用丁丙诺啡治疗母体OUD的患者进行结构化访谈，10名临床团队成员 以及5名研究小组成员。我们将向受访者介绍RCT方案，并要求 对基于共识的征聘能力、评估程序和可接受性标准的反馈。我们 将 解决方案， 要求受访者进行“事前分析”，以预测RCT失败的潜在病因，集思广益 并相应地调整RCT方案。在目标2中，我们将定量评估干预措施， 研究方法的可行性（例如，招募/保留目标的百分比，掩蔽的成功率，干预 保真度）和初步疗效，以最大限度地减少戒断症状， 标准丁丙诺啡诱导以治疗母体OUD（每组n=20）。结果将提供初步数据 帮助设计大型、多中心试验，以严格评估诱导方法对 重要的产科和新生儿结局。如果这项更大规模的试验表明， 该方案在多个人群中有效，该治疗方案可以广泛传播，以改善 母亲OUD患者及其婴儿的结局。