The Ohio Valley Node of the Clinical Trials Network

NIDA CTN方案0080 准妈妈阿片类药物使用障碍的药物治疗：一项实用的 比较缓释和每日丁丙诺啡制剂的随机试验 1.1研究目的 CTN？0080包括四个目标： * 目的：探讨阿片类药物使用障碍（OUD）对妊娠期妇女的影响 与舌下给药（SL）相比，接受缓释（XR）丁丙诺啡（BUP）的女性 BUP，关于母婴结局。假设的结果是，BUP-XR，相对 对于BUP-SL，集团将： 1)在妊娠期间没有更多的非法阿片类药物使用（主要，非劣效性）; 2)有较低的婴儿新生儿阿片类戒断综合征（NOWS）的严重程度（关键 次要，优效性）;以及 3)产后非法阿片类药物使用率没有增加（关键次要，非劣效性）。 * 次要目的：测试BUP-XR可能 与BUP-SL相比，改善母婴结局。 * 第三目的：确定使用BUP-XR相对于BUP-XR的经济价值。 SL，治疗孕妇。 * 第四章目的：评价BUP-XR相对于BUP-SL对婴儿的影响 神经发育 1.2研究设计 这是一项意向治疗、双臂、开放标签、实用的随机对照试验。资格 受试者将以1：1的比例随机分配至BUP-XR或BUP-SL，在研究中心进行平衡，估计 随机化时的胎龄（EGA）（6周-18周vs. 19周-30周），以及是否 在随机化时接受BUP-SL治疗（是vs.否）。将为参与者提供研究 产后12个月内每周接受一次药物治疗。参与者将被 邀请参加概念模型评估（CMA）子研究，该子研究将用于 评估MOM概念模型。婴儿护理人员将被邀请参加婴儿 神经发育结果（INO）子研究，其中包括24个月的儿童评估。的 INO数据将与CTN的其余部分分开锁定？0080数据库是否允许CTN？0080数据库 在收集最终（非INO）CTN-0080数据点后锁定。 1.3研究人群 从大约10个研究中心招募的大约200名妊娠女性将被随机分配至 审判在办公室环境中为孕妇提供BUP的场所提供BUP治疗 分娩后≥12个月，并接收足够的潜在合格女性以达到目标 随机化率（每月1.25）合格。研究人群将包括孕妇 随机化时EGA为6-30周，并且根据治疗提供者的判断， 适合BUP维持治疗。将鼓励所有随机化受试者 参与CMA和INO子研究。 1.4治疗 随机分配至BUP-XR组的受试者将在妊娠期间每周接受一次CAM 2038制剂。 在产后12个月期间，母乳喂养的妇女将继续接受BUP-XR 每周一次，而非母乳喂养的妇女将每月接受BUP-XR。随机化受试者 根据临床试验机构偏好，BUP-SL患者将在治疗期间接受丁丙诺啡，伴或不伴纳洛酮， 怀孕和产后12个月。 1.5评估 主要结局是妊娠期间非法阿片类药物戒断，通过尿液药物筛查进行评估 （UDS）。主要目的的关键次要结局是婴儿NOWS严重程度， 阿片类药物治疗天数（来自医疗记录）和母亲产后非法阿片类药物 由UDS评估的禁欲。CMA子研究包括以下评估：1）母体BUP谷值 研究第3周和第5周时的血浆浓度; 2）约36周时的胎儿非应激试验和生物物理学特征 母体BUP血浆峰浓度时的EGA周; 3）母体BUP血浆峰浓度和谷浓度 在约36周EGA;和4）分娩时脐带和母体血浆BUP/BUP代谢物水平。主要 经济结果将是增量成本效益比（ICER）。主要 INO子研究的神经发育结果将是贝利量表的认知子量表， 婴幼儿发展TM，第四版（BayleyTM-4），当孩子大约24岁时 月龄。 理想情况下，研究评估将在临床研究中心进行;但是，根据需要，这些访视可能在 全部或部分通过远程医疗，在其他机构附属的临床站点，或在其他地方， 社区（包括但不限于家访、其他非附属临床/实验室访视 网站，或其他社区网站提供适当的安全和保密性）的许可， 机构和其他管理机构。对于CMA和INO子研究，可能有些研究 手术将在诊所外的提供者认为最合适的地点进行 进行研究评估（包括但不限于分娩医院、外部 实验室或其他临床位置）。 1.6主要分析 非劣效性主要结局分析将使用α= 0.025的I类错误率。

NIDA CTN Protocol 0080 Medication treatment for Opioid use disorder in expectant Mothers (MOMs): a pragmatic randomized trial comparing extended-release and daily buprenorphine formulations 1.1 Study Objectives CTN?0080 includes four objectives: * Primary Objective: To evaluate the impact of treating opioid use disorder (OUD) in pregnant women with extended-release (XR) buprenorphine (BUP), compared to sublingual (SL) BUP, on mother and infant outcomes. Hypothesized outcomes are that the BUP-XR, relative to the BUP-SL, group will: 1) not have greater illicit opioid use during pregnancy (primary, non-inferiority); 2) have lower infant neonatal opioid withdrawal syndrome (NOWS) severity (key secondary, superiority); and 3) not have greater postpartum illicit opioid use (key secondary, non-inferiority). * Secondary Objective: To test conceptual models of the mechanisms by which BUP-XR may improve mother-infant outcomes, relative to BUP-SL. * Tertiary Objective: To determine the economic value of utilizing BUP-XR, relative to BUP- SL, to treat pregnant women. * Quaternary Objective: To evaluate the impact of BUP-XR, relative to BUP-SL, on infant neurodevelopment. 1.2 Study Design This is an intent-to-treat, two-arm, open-label, pragmatic randomized controlled trial. Eligible participants will be randomized in a 1:1 ratio to BUP-XR or BUP-SL, balancing on site, estimated gestational age (EGA) at time of randomization (6 weeks-18 weeks vs. 19 weeks-30 weeks), and whether they are on BUP-SL at the time of randomization (yes vs. no). Participants will be provided with study medication and attend weekly medication visits through 12 months postpartum. Participants will be invited to participate in the conceptual model assessment (CMA) sub-study, which will be used to evaluate the MOMs conceptual models. Infant caregivers will be invited to participate in the infant neurodevelopmental outcomes (INO) sub-study, which will include a 24-month child assessment. The INO data will be locked separately from the rest of the CTN?0080 database to allow CTN?0080 database lock following collection of the final (non-INO) CTN-0080 data point. 1.3 Study Population Approximately 200 pregnant women, recruited from approximately 10 sites, will be randomized into the trial. Sites that provide BUP to pregnant women in an office-based setting, offer BUP treatment following delivery for ≥12 months, and admit enough potentially eligible women to meet the target randomization rate (1.25 per month) are eligible. The study population will include pregnant women who have an EGA of 6-30 weeks at randomization, and, in the judgment of the treating provider, are good candidates for BUP-maintenance treatment. All randomized participants will be encouraged to participate in the CMA and INO sub-studies. 1.4 Treatments Participants randomized to BUP-XR will receive a weekly formulation of CAM2038 during pregnancy. During the 12-month postpartum phase, women who are breastfeeding will continue receiving BUP-XR weekly while women who are not breastfeeding will receive monthly BUP-XR. Participants randomized to BUP-SL will receive buprenorphine, with or without naloxone, based on site preference, during pregnancy and the 12-month postpartum phase. 1.5 Assessments The primary outcome is illicit opioid abstinence during pregnancy, assessed by urine drug screens (UDSs). Key secondary outcomes for the primary objective are infant NOWS severity assessed by total days of opioid treatment (derived from medical records), and mother postpartum illicit opioid abstinence assessed by UDSs. The CMA sub-study includes assessments of: 1) maternal trough BUP plasma concentrations at study weeks 3 and 5; 2) fetal non-stress test and biophysical profile at ~36 weeks EGA at maternal peak BUP plasma level; 3) maternal peak and trough BUP plasma concentrations at ~36 weeks EGA; and 4) cord and maternal plasma BUP/BUP-metabolite levels at delivery. The main economic outcome will be the incremental cost-effectiveness ratio (ICER). The main neurodevelopmental outcome of the INO sub-study will be the cognitive subscale of the Bayley Scales of Infant and Toddler DevelopmentTM, Fourth Edition (BayleyTM-4) when the child is approximately 24 months of age. Study assessments will ideally occur at the clinic site; however, as needed these visits may occur in whole or in part via telemedicine, at other institutionally-affiliated clinical sites, or elsewhere in the community (including, but not limited to, home visits, visits at other non-affiliated clinical/laboratory sites, or other community sites affording appropriate safety and confidentiality) as permitted by the institution and other regulatory bodies. For the CMA and INO sub-studies, it is likely that some study procedures will occur outside the clinic at locations deemed most appropriate by the providers performing the study assessments (including, but not limited to, the delivery hospital, an external laboratory, or other clinical location). 1.6 Primary Analysis A Type-I error rate of α=.025 will be used for the non-inferiority primary outcome analysis.