The Ohio Valley Node of the Clinical Trials Network

临床试验网络俄亥俄谷节点

• 批准号: 10441986
• 负责人: T John WINHUSEN
• 金额: $ 90.04万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10441986
• 关键词: Abstinence; Age-Months; Biophysics; Breast Feeding; Buprenorphine; Caregivers; Child; Clinic; Clinical; Clinical Trials Network; Cognitive; Collection; Communities; Data; Databases; Drug Screening; Epidemic; Equilibrium; Formulation; Gestational Age; Health; Home visitation; Hospital Costs; Hospitals; Infant; Institution; Judgment; Laboratories; Location; Maintenance; Medical Records; Modeling; Mothers; Naloxone; National Institute of Drug Abuse; Neonatal Abstinence Syndrome; Ohio; Opioid; Outcome; Participant; Pharmaceutical Preparations; Phase; Plasma; Postpartum Period; Pregnancy; Pregnant Women; Prevalence; Procedures; Protocols documentation; Provider; Randomized; Randomized Controlled Trials; Research Design; Rest; Safety; Severities; Site; Telemedicine; Testing; Time; Toddler; Urine; Visit; Woman; arm; base; buprenorphine treatment; clinical research site; cost-effectiveness ratio; economic outcome; economic value; eligible participant; fetal; illicit opioid; improved; incremental cost-effectiveness; infant outcome; neurodevelopment; open label; opioid use; opioid use disorder; preference; primary outcome; randomized trial; recruit; secondary outcome; study population; trial comparing

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.

NIDA CTN协议0080 准妈妈（MOM）阿片类药物使用障碍的药物治疗：务实的 比较缓释剂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： * 主要目标：评估治疗阿片类药物使用障碍 (OUD) 对孕妇的影响 与舌下含服 (SL) 相比，使用缓释 (XR) 丁丙诺啡 (BUP) 的女性 BUP，关于母亲和婴儿的结局。假设结果是 BUP-XR，相对 对于 BUP-SL，小组将： 1) 怀孕期间没有更多地非法使用阿片类药物（主要、非劣效性）； 2) 婴儿新生儿阿片戒断综合征 (NOWS) 严重程度较低（关键 次要的、优越的）；和 3) 产后没有更多的非法阿片类药物使用（关键次要，非劣效性）。 *次要目标：测试 BUP-XR 可能作用机制的概念模型 相对于 BUP-SL 可以改善母婴结局。 * 第三个目标：确定使用 BUP-XR 相对于 BUP- 的经济价值 SL，用于治疗孕妇。 * 第四个目标：评估 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、务实的随机对照试验。有资格的 参与者将按 1:1 的比例随机分配至 BUP-XR 或 BUP-SL，现场平衡，估计 随机分组时的孕龄 (EGA)（6 周至 18 周与 19 周至 30 周），以及是否 他们在随机分组时服用 BUP-SL（是与否）。参与者将获得学习 药物治疗，并在产后 12 个月内每周进行药物访视。参加者将是 受邀参加概念模型评估（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。这 INO 数据将与 CTN?0080 数据库的其余部分分开锁定，以允许 CTN?0080 数据库 锁定以下最终（非 INO）CTN-0080 数据点的收集。 1.3 研究人群 从约 10 个地点招募的约 200 名孕妇将被随机分配到 审判。在办公室环境中向孕妇提供 BUP 的网站提供 BUP 治疗 分娩后≥12个月，并接纳足够多的潜在合格女性以达到目标 随机化率（每月 1.25）符合条件。研究人群将包括孕妇 随机分组的 EGA 为 6-30 周，并且根据治疗提供者的判断， BUP 维持治疗的良好候选者。将鼓励所有随机参与者 参与CMA和INO子研究。 1.4 治疗 随机接受 BUP-XR 治疗的参与者将在怀孕期间每周接受一次 CAM2038 制剂。 在产后 12 个月期间，母乳喂养的女性将继续接受 BUP-XR 每周一次，而非母乳喂养的女性则每月接受一次 BUP-XR。参与者随机分组 BUP-SL 将根据地点偏好在有或没有纳洛酮的情况下接受丁丙诺啡， 怀孕和产后 12 个月阶段。 1.5 评估 主要结局是妊娠期间非法阿片类药物戒断，通过尿液药物筛查评估 （UDS）。主要目标的关键次要结局是按总人数评估的婴儿NOWS 严重程度 阿片类药物治疗天数（来自医疗记录）以及母亲产后非法阿片类药物 由 UDS 评估的戒断情况。 CMA 子研究包括以下评估： 1) 产妇 BUP 谷值 研究第 3 周和第 5 周的血浆浓度； 2) 胎儿无压力测试和生物物理特征~36 母体血浆 BUP 峰值水平的 EGA 周数； 3) 母体BUP血浆浓度峰值和谷值 约 36 周 EGA； 4) 分娩时脐带和母体血浆 BUP/BUP 代谢物水平。主要 经济成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分量表 婴儿和幼儿发展TM，第四版（BayleyTM-4），当孩子大约24岁时 月龄。 研究评估最好在诊所进行；然而，根据需要，这些访问可能会发生在 全部或部分通过远程医疗、在其他机构附属的临床地点或在其他地方进行 社区（包括但不限于家访、访问其他非附属临床/实验室） 网站或其他提供适当安全性和保密性的社区网站） 机构和其他监管机构。对于 CMA 和 INO 子研究，一些研究可能 程序将在诊所外、医疗服务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 实验室或其他临床场所）。 1.6 初步分析 α=0.025 的 I 类错误率将用于非劣效性主要结果分析。