A randomised trial of the pro-phylactic use of melatonin in critically ill patients to evaluate if this leads to a reduction in incidence of delirium (Pro-MEDIC study)

Rationale Delirium is defined as acute organic brain dysfunction characterised by inattention and disturbance of cognition. It is common in the intensive care unit and is associated with poorer outcomes. Good quality sleep is important in the prevention and management of delirium. Melatonin is a natural hormone secreted by the pineal gland which helps in the regulation of the sleep-wake cycle. It is possible that melatonin supplementation in intensive care improves sleep and prevents delirium. Methods and design The 'Prophylactic Melatonin for Delirium in Intensive Care' study is a multi-centre, randomised, double-blinded, placebo-controlled trial. The primary objective of this study is to determine whether melatonin given prophylactically decreases delirium in critically ill patients. A total of 850 ICU patients have been randomised (1:1) to receive either melatonin or a placebo. Participants were monitored twice daily for symptoms of delirium. Results This paper and the attached additional files describe the statistical analysis plan (SAP) for the trial. The SAP has been developed and submitted for publication before the database has been locked and before the treatment allocation has been unblinded. The SAP contains details of analyses to be undertaken, which will be reported in the primary and secondary publications.

研究背景
谵妄（Delirium）被定义为以注意力不集中与认知障碍为特征的急性器质性脑功能障碍。该病症在重症监护病房中高发，且与不良临床预后密切相关。优质睡眠对于谵妄的预防及临床管理至关重要。褪黑素是由松果体分泌的天然激素，可参与调节机体睡眠-觉醒周期。据此推测，在重症监护场景中补充褪黑素或可改善患者睡眠质量，进而预防谵妄发生。

研究方法与设计
本项命名为「重症监护病房谵妄预防性褪黑素治疗」的研究为多中心、随机、双盲、安慰剂对照临床试验。本研究的主要目标为明确预防性给予褪黑素是否可降低重症患者的谵妄发生率。研究共纳入850名重症监护病房（Intensive Care Unit, ICU）患者，按1:1比例随机分配至褪黑素干预组与安慰剂对照组。所有受试者每日接受两次谵妄症状监测。

研究结果
本文及附带的附加文件详细阐述了本临床试验的统计分析计划（Statistical Analysis Plan, SAP）。该统计分析计划已于数据库锁定、治疗分配揭盲前完成制定并提交发表。计划中涵盖了所有待执行的分析细节，相关分析结果将在本研究的主要及次要成果出版物中正式报告。