Maternal Opioid Treatment: Human Experimental Research

描述（由申请人提供）： 虽然明显有益，但在妊娠期间使用美沙酮仍然存在争议，部分原因是大比例的新生儿具有阿片样物质戒断症状，需要医疗干预和延长住院时间。一种新药丁丙诺啡被美国食品和药物管理局（FDA）批准用于治疗非妊娠阿片类药物依赖患者，并且在突然停药后仅产生轻度戒断综合征。来自约翰霍普金斯医学院（JHUSOM）的一项双盲随机试验的有希望的初步数据表明，与美沙酮相比，丁丙诺啡可改善出生结局，减少新生儿戒断体征（NAS）。目前的随机、平行组研究将是第一个多中心试验，以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。佛蒙特大学（UVM）研究中心提议参与由JHUSOM牵头的多中心试验，该试验涉及另外四个美国研究中心和两个国际研究中心。为此，我们汇集了一个在精神病学，成瘾医学，产科和妇科学方面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，并为研究提供严格的科学专业知识。在UVM研究中心，阿片类药物依赖的孕妇将被随机分配至最佳剂量的美沙酮（n=24）或丁丙诺啡（n=24），并在整个妊娠期间进行随访。将比较治疗组的主要结局指标：峰值总NAS评分;接受NAS治疗的新生儿数量;接受NAS治疗的新生儿接受的抗戒断药物总量;头围;新生儿住院时间。次级新生儿/胎儿结局指标包括其他身体、行为和安全参数。次要孕产妇结局包括治疗保留、药物使用、药物安全性、心理社会功能和剂量充足性。UVM研究中心的独特之处在于，将在研究参与者和胎龄匹配的社区志愿者之间比较延迟折扣。这项研究的结果有可能提供重要的见解，为什么一些孕妇滥用阿片类药物，尽管可能对胎儿造成潜在的伤害。UVM研究中心拥有独特的专业知识、经验和资源，可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中开展临床试验（即，吸毒孕妇）。总体而言，这项研究将为FDA提供关键数据，以支持妊娠期间使用丁丙诺啡的适应症，并可能优化安全有效治疗妊娠阿片类药物依赖女性的策略。

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.