Maternal Opioid Treatment: Human Experimental Research

描述(由申请人提供)： 尽管美沙酮显然是有益的，但在怀孕期间使用美沙酮仍然存在争议，部分原因是L N有很大比例的新生儿有阿片类药物戒断的迹象，需要医疗干预和延长住院时间。美国食品和药物管理局(FDA)批准了一种名为丁丙诺啡的新药，用于治疗非怀孕的阿片依赖患者，在突然戒断后只会产生轻微的戒断综合症。]约翰斯·霍普金斯医学院(JHUSOM)的一项双盲随机试验的初步数据显示，与美沙酮相比，丁丙诺啡可以改善分娩结局，减少新生儿禁欲症状(NAS)。目前的随机平行小组研究将是第一次评估丁丙诺啡相对于美沙酮在阿片类药物依赖孕妇中减少NAS的疗效的多点试验。佛蒙特州大学(UVM)网站提议参加由JHUSOM牵头的多站点试验，涉及另外四个美国站点和两个国际站点。为此，我们汇集了一支在精神病学、成瘾药物、产科和新生儿学方面接受过培训的多学科团队，他们具有专业知识，为参与者提供全面的护理和严谨的科学知识。在UVM地点，阿片依赖孕妇将被随机分配到最佳剂量的美沙酮(n=24)或丁丙诺啡(n=24)，并在整个怀孕期间进行跟踪。治疗组将在以下主要结果指标上进行比较：NAS总分峰值；接受NAS治疗的新生儿数量；接受NAS治疗的新生儿给予的抗戒断药物总量；头围；以及新生儿住院时间。二次新生儿/胎儿结局测量包括其他生理、行为和安全参数。次要的孕产妇结果包括治疗保留、药物使用、用药安全性、心理社会功能和剂量充分性。UVM网站独有的延迟折扣将在研究参与者和胎龄匹配的社区志愿者之间进行比较。这项针对特定部位的研究结果有可能为一些孕妇滥用阿片类药物提供重要的见解，尽管这可能对胎儿造成潜在的伤害。UVM网站拥有独特的专业知识、经验和资源，可以为这一新的潜在网络做出贡献，该网络旨在在难以招募的人群(即吸毒孕妇)中进行临床试验。总体而言，这项研究将为FDA提供关键数据，以支持孕期使用丁丙诺啡的适应症，并可能优化安全有效地治疗怀孕阿片依赖妇女的策略。

DESCRIPTION (provided by applicant): Though clearly beneficial, the use of methadone during pregnancy remains controversial due in part to the large l N percentage of newborns having signs of opioid withdrawal requiting medical intervention and extended hospitalization. A new medication, Buprenorphine, is approved by the Food and Drug Administration (FDA) for the treatment of non-pregnant opioid-dependent patients and produces only a mild abstinence syndrome following abrupt withdrawal.] Promising preliminary data from a double-blind randomized trial at the Johns Hopkins School of Medicine (JHUSOM) suggest that buprenorphine results in improved birth outcomes and fewer neonatal abstinence signs (NAS) relative to methadone. The current randomized, parallel group study will be the first multi-site trial to assess the efficacy of buprenorphine for reducing NAS relative to methadone in opioid-dependent pregnant women. The University of Vermont (UVM) site proposes to participate in the multi-site trial lead by JHUSOM involving four other U.S. and two international sites. To do so, we have brought together a multidisciplinary team trained in psychiatry, addiction medicine, obstetrics, and neonatology with the professional expertise to provide comprehensive care for the participants and rigorous scientific expertise for the study. At the UVM site, opioid-dependent pregnant women will be randomized to optimal doses of methadone (n=24) or buprenorphine (n=24) and followed throughout pregnancy. Treatment groups will be compared on the primary outcome measures of peak total NAS score; number of neonates treated for NAS; total amount of anti-withdrawal medication given to neonates treated for NAS; head circumference; and neonatal length of hospital stay. Secondary neonatal/fetal outcome measures include other physical, behavioral and safety parameters. Secondary maternal outcomes include treatment retention, drug use, medication safety, psychosocial functioning and dose adequacy. Unique to the UVM site, delay discounting will be compared between study participants and gestational age matched community volunteers. The results of this site-specific study have the potential to provide important insights into why some pregnant women abuse opiates despite the potential harm that may do to the fetus. The UVM site has unique expertise, experience and resources to contribute to this new potential network designed to conduct clinical trials in a difficult to recruit population (i.e., drug-abusing pregnant women). Overall, this study will provide pivotal data to the FDA to support an indication for the use of buprenorphine during pregnancy and potentially optimize strategies for safe and effective treatment of pregnant opioid-dependent women.