A Randomized Double Blind Placebo Controlled Trial of Ramelteon in the Prevention of Post-operative Delirium in Older Patients Undergoing General Anesthesia

雷美替胺预防接受全身麻醉的老年患者术后谵妄的随机双盲安慰剂对照试验

• 批准号: 9336229
• 负责人: Karin Jane Neufeld
• 金额: $ 20.25万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9336229
• 关键词: Acute; Adherence; Adult; Adverse effects; Adverse event; Affect; Aging; Agonist; Amyloid; Anesthesia procedures; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Biological; Caring; Circadian Rhythms; Clinical; Cognitive; Confusion; Consensus; Controlled Clinical Trials; DSM-V; Day Surgery; Delirium; Detection; Diagnosis; Distress; Dopamine; Dose; Double-Blind Method; Drowsiness; Elderly; Ensure; Family; Fatigue; Funding Mechanisms; General Anesthesia; Goals; Headache; Health Care Costs; Healthcare; Healthcare Systems; Hip Joint; Hospitalization; Impaired cognition; Incidence; Individual; Institutionalization; Intervention; Knee joint; Length of Stay; Maintenance; Medical; Melatonin; Methodology; Operative Surgical Procedures; Oral; Orthopedics; Outcome; Patients; Perioperative; Pharmaceutical Preparations; Phase; Phase III Clinical Trials; Physiological; Placebos; Population; Postoperative Period; Prevention; Prevention trial; Preventive; Public Health; Randomized; Randomized Controlled Trials; Reconstructive Surgical Procedures; Recovery; Reporting; Risk; Safety; Serious Adverse Event; Single-Blind Study; Sleep; Sleep Disorders; Sleep Wake Cycle; Sleeplessness; Symptoms; Testing; Work; active method; aged; cohort; cost; double-blind placebo controlled trial; high risk population; improved; innovation; mental state; mortality; neuroinflammation; older patient; patient population; phase II trial; postoperative delirium; prevent; primary outcome; randomized placebo controlled trial

Postoperative delirium, an acute confusional state caused by an underlying physiological disturbance following surgery and characterized by sleep/wake cycle disturbances, is a serious public health problem that disproportionately affects older people, particularly those with underlying cognitive impairment. Delirium is associated with many negative outcomes including: increased mortality, longer hospital stays, increased institutionalization after acute care hospitalization, worse cognitive and physical outcomes (both short- and long-term), and significant distress for patients and their families. Estimates of healthcare costs due to all episodes of delirium among the elderly range from $38 to $152 billion/year. Aging of the population means increasing numbers of older adults are undergoing surgery – making postoperative delirium prevention an urgent priority. This proposal provides innovation by examining the delirium preventive effects of the melatonin agonist, ramelteon, by conducting a randomized, double blind controlled clinical trial in 80 adults, >65 years, undergoing planned orthopaedic reconstructive surgery of non-infected knee or hip joint under general anesthesia. Ramelteon/placebo will be administered orally the evening before surgery and at bedtimes on the day of surgery and postoperative day (POD) 1. The specific aims of this exploratory phase II trial include the comparison of 1) postoperative delirium incidence, and 2) adverse events in active treatment and placebo. Delirium prevention may occur through multiple mechanisms including maintenance of sleep and diurnal rhythms, anti-inflammatory effects, and/or dopamine blockade. In addition, the proposal examines both early (PACU) and late (POD 1 and 2) effects of ramelteon on postoperative delirium prevention. A positive trial will have substantial clinical and public health impact by offering an easy-to-use and safe perioperative intervention to prevent postoperative delirium in older surgical patients and guiding translational work to explore new mechanisms in the understanding the causes of postoperative delirium.

后代del妄，这是一种急性混乱状态 手术后的身体障碍，以睡眠/唤醒周期为特征 干扰是一个严重的公共卫生问题，对老年人的影响不成比例 人们，特别是那些具有潜在认知障碍的人。 del妄是相关的 有许多负面结果，包括：死亡率增加，住院时间更长， 急性护理住院治疗后的机构化增加，认知能力较差和 身体结局（短期和长期），以及患者的严重困扰， 他们的家人。估计由于所有del妄的医疗费用估计 老年人/年不等38美元至1520亿美元。人口老龄化意味着增加 老年人的人数正在接受手术 - 术后del妄 预防紧急优先事项。 该提案通过检查 褪黑激激动剂Ramelteon，通过进行随机的双盲控制 经历了计划的骨科重建，> 65岁，> 65岁，> 65岁 全身麻醉下未感染的膝盖或髋关节的手术。 Ramelteon/安慰剂 将在手术前的晚上和时间进行口头管理 手术和术后日（POD）1。该探索性II期的具体目的 试验包括1）术后ir妄发病率的比较，2）不利 主动治疗和安慰剂中的事件。预防ir妄可能通过多个 机制，包括维持睡眠和昼夜节奏，抗炎 效果和/或多巴胺封锁。此外，提案考试既早点又 Ramelteon对术后del妄的（PACU）和晚期（POD 1和2）影响 预防。积极的试验将对 提供易于使用且安全的周期性干预措施，以防止术后 老年外科患者的ir妄，并指导翻译工作以探索新的 理解术后del妄的原因的机制。