Incorporating nonpharmacologic approaches into a comparative effectiveness pharmacologic trial for neonates with neonatal opioid withdrawal syndrome (NOWS)

将非药物方法纳入新生儿阿片戒断综合征 (NOWS) 新生儿的比较有效性药理学试验

• 批准号: 10380398
• 负责人: Gregory M. Sokol
• 金额: $ 46.89万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10380398
• 关键词: Academic Medical Centers; Accounting; Admission activity; Age; Area; Basic Science; Behavior; Birth; Buprenorphine; Caregivers; Caring; Cellular biology; Child; Childhood; Clinical; Clinical Research; Clinical Research Protocols; Clinical Services; Clinical Trials; Clinical and Translational Science Awards; Collaborations; Conduct Clinical Trials; Critical Illness; Data; Development; Diagnosis; Dose; Enrollment; Environment; Evaluation; Faculty; Familiarity; Follow-Up Studies; Genomics; Health; Hospitals; Indiana; Individual; Infant; Infant Care; Intervention; Investigation; Knowledge; Leadership; Length of Stay; Link; Measures; Medical Research; Methadone; Methodist Church; Methods; Morphine; Mothers; Multicenter Neonatal Research Network; National Institute of Child Health and Human Development; Neonatal; Neonatal Abstinence Syndrome; Newborn Infant; Nurseries; Outpatients; Patients; Pediatric Hospitals; Pediatric Research; Perinatal; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Pharmacotherapy; Population; Pregnant Women; Principal Investigator; Proteomics; Protocols documentation; Pulmonary Hypertension; Randomized; Randomized Controlled Trials; Research; Research Activity; Research Infrastructure; Research Methodology; Research Personnel; Respiratory Failure; Role; Schedule; Scientific Inquiry; Screening procedure; Standardization; Symptoms; Time; Translational Research; Universities; Urban Hospitals; Weaning; Withdrawal; Withdrawal Symptom; Woman; arm; biomedical referral center; clinical center; comparative effectiveness; comparative effectiveness trial; design; effectiveness clinical trial; experience; falls; follow-up; high risk; improved; inhaled nitric oxide; inner city; innovation; medical schools; neonatal care; neonate; novel; opioid epidemic; patient population; prevent; programs; reduce symptoms; research study; service delivery; standardized care; stem cells; treatment strategy

PROJECT SUMMARY / ABSTRACT The nationwide opioid epidemic includes women of child birthing age accounting for a dramatically increased number of infants being born with neonatal opioid withdrawal syndrome (NOWS). Currently there is no uniformly accepted treatment strategy for NOWS and the choice of primary medication, criteria for treatment, and dosing/weaning schedules vary between centers. Morphine is by far the most commonly used medication for NOWS treatment, followed by methadone. Buprenorphine is a promising drug but with limited studied in this patient population. Additionally, the screening tools used to diagnose NOWS and the appropriate threshold to initiate drug therapy have not been conclusively evaluated. When historical empirically derived drug treatment and weaning protocols have been modified and standardized, reductions of length of stay have been observed. Additionally, nonpharmalogical methods appear to be successful in reducing the symptoms of NOWS. In this application we present preliminary data of a pilot randomized controlled trial currently in progress in our nursery. It includes identifying infants with severe symptoms of NOWS via modified Finnegan scoring, then randomizing them to a standard morphine dosing/weaning schedule, or to an optimal morphine dosing strategy. The optimal morphine dosing strategy does not provide a scheduled dose of morphine, but only provides a dose of morphine when the withdrawal symptoms cannot be satiated through nonpharmacological means. Both study groups received all optimized nonpharmacological methods available to them. In the optimal morphine arm, we observed a large reduction in the use of morphine and in the duration of days receiving pharmacologic therapy. We speculate that the use of the optimal morphine dosing strategy limited the use of pharmacologic treatment to only times when nonpharmacologic interventions were not sufficient. This essentially provided the mother or other care givers time to recognize and adapt to the infant's withdrawal behaviors, enabling them to extinguish them via nonpharmacological means. The optimal morphine dosing strategy also prevented the infant's withdrawal from becoming too symptomatic by allowing morphine to be used when needed, yet not committing the infant to a prolonged scheduled course of morphine treatment and weaning when nonpharmacological measures could have sufficed. Thus, we favor a clinical trial that emphasizes the use of nonpharmacological methods to control withdrawal symptoms irrespective of the drug arm the infant is assigned. However, we favor including a more novel optimal dosing strategy arm rather than limiting the investigation to standard scheduled dosing/weaning arms.

项目摘要/摘要 全国范围内的阿片类药物流行包括育龄妇女占戏剧性的 出生时患有新生儿阿片戒断综合征(NOWS)的婴儿数量增加。目前在那里 NOWS的治疗策略和初级药物的选择是否没有统一的标准 治疗和给药/断奶计划在不同的中心有所不同。到目前为止，吗啡是最常见的 使用药物治疗NOWS，其次是美沙酮。丁丙诺啡是一种很有前途的药物，但 在这一患者群体中进行的研究有限。此外，用于诊断NOWS和 启动药物治疗的合适阈值尚未得到最终评估。当具有历史意义时 经验性衍生药物治疗和断奶方案已经修改和标准化，减少了 已经观察到了停留时间的长短。此外，非药理学方法似乎在 减轻NOWS的症状。在本申请中，我们提供了一种随机试验的初步数据 我们的托儿所目前正在进行对照试验。它包括识别有严重症状的婴儿 现在通过改良的芬尼根评分，然后将他们随机分配到标准的吗啡剂量/断奶 时间表，或一个最佳的吗啡剂量策略。最佳的吗啡剂量策略不会 提供预定剂量的吗啡，但只在戒断时提供一定剂量的吗啡 症状不能通过非药物手段来缓解。两个研究组都接受了优化 他们可以使用非药理学的方法。在最佳的吗啡臂中，我们观察到了大量的 减少吗啡的使用和接受药物治疗的天数。我们推测 最佳吗啡给药策略的使用将药物治疗的使用仅限于 非药物干预不充分的时候。这基本上提供了母亲或 其他照顾者有时间识别并适应婴儿的回避行为，使他们能够 通过非药物手段消灭它们。最佳的吗啡剂量策略也防止了 婴儿戒断变得太有症状，允许在需要时使用吗啡，但不是 让婴儿接受长时间的吗啡治疗，并在下列情况下断奶 非药物措施本可以满足需要。因此，我们倾向于临床试验，强调使用 控制戒断症状的非药物方法，无论婴儿使用的是哪种药物 已分配。然而，我们倾向于包括更新的最优剂量策略ARM，而不是限制 对标准的预定剂量/断奶手臂进行调查。