Maternal Opioid Treatment: Human Experimental Research

描述（由申请人提供）： 虽然明显有益，但在怀孕期间使用美沙酮仍然存在争议，部分原因是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。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）的双盲随机试验的有希望的初步数据直接告知了这一修订后的申请，并表明丁丙诺啡导致出生结局改善和新生儿戒断综合征（NAS）相对于美沙酮。目前的随机化，平行组研究将是第一个多中心试验，以评估阿片类药物依赖的孕妇丁丙诺啡相对于美沙酮减少NAS的疗效。JHUSOM是本研究的牵头研究中心，涉及6家美国研究中心和2家国际研究中心。JHUSOM团队在成瘾医学，精神病学，儿科，产科，妇科和对照临床试验方面接受过培训，将确保对研究进行全面监督和严格的科学完整性。阿片类药物依赖的孕妇将随机接受最佳剂量的美沙酮（n=30）或丁丙诺啡（n=30），并在整个妊娠期进行随访。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;头围的物理出生参数;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。这第一项研究将建立一个基础设施和网络，为1号物质滥用/依赖孕妇进行药物治疗的对照试验提供专门知识。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 in part to the large percentage of newborns having signs of opioid withdrawal requiring 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) have informed directly this revised application and suggest that buprenorphine results in improved birth outcomes and less neonatal abstinence syndrome (NAS) relative to methadone. The current randomized, parallel group study will be the first multi-site trial to assess in opioid-dependent pregnant women the efficacy of buprenorphine for reducing NAS relative to methadone. JHUSOM is the Lead Site for this study involving six United States and two international sites. The JHUSOM team trained in addiction medicine, psychiatry, pediatrics, obstetrics, neonatology, and controlled clinical trials will assure comprehensive oversight and rigorous scientific integrity of the study. Opioid-dependent pregnant women will be randomized to optimal doses of methadone (n=30) or buprenorphine (n=30) 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; physical birth parameter of 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. This first study will establish an infrastructure and network with expertise in conducting controlled trials with pharmacotherapies for substance 1busing/dependent 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.