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.

### 研究依据
谵妄（Delirium）被定义为以注意力障碍与认知紊乱为特征的急性器质性脑功能障碍。该病症在重症监护病房（Intensive Care Unit，ICU）中高发，且与更差的临床预后相关。优质睡眠对于谵妄的预防与管理至关重要。褪黑素（Melatonin）是由松果体分泌的天然激素，可调控睡眠-觉醒周期。据此推测，在重症监护期间给予褪黑素补充治疗或可改善患者睡眠状况，进而预防谵妄发生。

### 研究方法与设计
"重症监护病房谵妄预防性褪黑素治疗"（Prophylactic Melatonin for Delirium in Intensive Care）研究为一项多中心、随机、双盲、安慰剂对照试验。本研究的主要目标为明确预防性给予褪黑素是否能够降低重症患者的谵妄发生率。研究共纳入850名ICU患者，按1:1比例随机分配至褪黑素组与安慰剂组。受试者每日接受两次谵妄症状监测。

### 研究结果
本论文及附属补充文件阐述了该试验的统计分析计划（Statistical Analysis Plan，SAP）。该计划已于数据库锁定及治疗分配揭盲前完成制定并投稿待发表，涵盖了所有待实施的分析细节，相关结果将刊载于主刊及副刊出版物中。