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 怀孕期间阿片类药物使用障碍（OUD）的患病率正在上升，增加了严重的事件 尽管母体，新生儿和产科发病率和死亡率。尽管可以有效地治疗母亲 借助丁丙诺啡，导致对产前护理的依从性提高并减少了产科并发症， 五分之一的患者中有不到1例接受了母体OUD的药物治疗。在很大程度上，很少的孕妇 接受丁丙诺啡是有效启动的挑战。启动（称为丁丙诺啡 由于目前的撤回，归纳必须开始现代。如果诱导开始得太早，丁丙诺啡将 从μ受体中取代其他阿片类药物，导致严重戒断。孕产妇的戒断 沉淀和预期，与高继电器率，不遵守和较低的治疗保留有关 费率。毫不奇怪，诱导是OUD治疗中辍学的已知关键时间点。多个替代方案 据报道，丁丙诺啡诱导方案，包括不需要的成功方法 通过使用丁丙诺啡的微量质糖，例如通过A 透皮贴片，作为完全舌下剂量的桥梁感应方法。但是，丁丙诺啡诱导 在怀孕中，方案从未研究过以确定最有效的类型。我们提出了一个潜在的 在两个特异性产前诊所的混合方法研究，以评估进行随机的可行性 对照试验（RCT）比较丁丙诺啡透明桥与标准舌下 孕妇OUD诱导。在AIM 1中，我们将使用半数评估可行性域 使用丁丙诺啡治疗材料OUD的20名患者的结构化访谈，10名临床团队成员 对待他们的人和5名研究小组成员。我们将向受访者介绍RCT协议，并要求 招聘能力，评估程序和可接受性的基于共识的标准的反馈。我们 将要 解决方案， 要求受访者进行“前列性”练习，以预测RCT失败，头脑风暴的潜在病因 并相应地调整RCT协议。在AIM 2中，我们将定量评估干预措施和 研究方法可行性（例如，招聘/保留目标的百分比，掩盖成功，干预 保真度）和初步效率，以通过进行桥梁的飞行员RCT与 标准丁丙诺啡诱导以治疗材料OUD（每臂n = 20）。结果将提供初步数据 帮助设计大型多站点试验，以严格评估诱导方法的效率 重要的产科和新生儿结果。如果该较大的试验表明桥丁丙诺啡感应 协议在多个人群中有效，该治疗方案可以广泛传播以改进 Mater Oud及其婴儿的患者的结局。