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 孕产妇、新生儿和产科发病率和死亡率。尽管母体OUD可以得到有效的治疗 丁丙诺啡可提高产前护理的依从性，减少产科并发症， 只有不到1/5的患者接受母体OUD的药物治疗。在很大程度上，怀孕的女性很少 接受丁丙诺啡，因为它可能是有效启动的挑战。起始期(称为丁丙诺啡 诱导)必须在患者处于适度戒断状态时开始。如果引产开始得太早，丁丙诺啡 取代μ受体上的另一种阿片类药物，导致严重的戒断。母性戒断，两者都是 沉淀和预期，与高复发率、不坚持和较低的治疗保留率有关 费率。不足为奇的是，在OUD治疗中，诱导是一个已知的退出的关键时间点。多个备选方案 已经报道了丁丙诺啡诱导的方案，包括成功的不需要 通过使用小剂量丁丙诺啡，如通过 透皮贴剂，作为一种过渡诱导方法，达到全舌下剂量。然而，丁丙诺啡诱导 在怀孕期间，从未研究过确定最有效的类型的方案。我们提出了一种前瞻性的， 在两个专门的产前诊所进行的混合方法研究，以评估进行随机调查的可行性 丁丙诺啡透皮桥诱导与标准舌下注射的对照试验 妊娠合并胎儿宫内窘迫患者的诱导。在目标1中，我们将定性地评估可行域使用半 对20名使用丁丙诺啡治疗产妇的患者进行结构化访谈，10名临床团队成员 谁来治疗他们，以及5名研究团队成员。我们将向受访者介绍随机对照试验方案，并要求 对招聘能力、评估程序和可接受性的协商一致标准的反馈。我们 将要 解决方案， 让受访者进行一次“临终前”练习，以预测RCT失败的潜在原因，头脑风暴 并相应地调整RCT协议。在目标2中，我们将定量评估干预措施和 研究方法的可行性(例如，招募/保留目标的百分比、掩饰成功、干预 保真度)和初步疗效，以最大限度地减少戒断症状，通过进行桥接与 丁丙诺啡标准诱导用于治疗母婴(每臂20例)。结果将提供初步数据 协助设计大型、多部位试验，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丁丙诺啡诱导桥 方案在多个人群中有效，这种治疗方案可以广泛传播以改进 母体脐带血及其婴儿的结局。