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，在突然停药后只会产生轻微的戒断综合征。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为这一修订后的申请提供了信息，并表明丁丙诺啡与美沙酮相比可以改善分娩结果并减少新生儿禁欲综合征(NAS)。目前的随机、平行分组研究将是第一次在阿片依赖孕妇中评估丁丙诺啡相对于美沙酮减少NAS的有效性的多点试验。JHUSOM是这项研究的牵头站点，涉及六个美国站点和两个国际站点。JHUSOM团队在成瘾药物、精神病学、儿科、产科、新生儿学和受控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。阿片依赖孕妇将被随机分配到最佳剂量的美沙酮(n=30)或丁丙诺啡(n=30)，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；头围的体格出生参数；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。这项第一项研究将建立一个基础设施和网络，在对1号物质妊娠/依赖的孕妇进行药物疗法的对照试验方面具有专业知识。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 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.