Title page Impact of oral melatonin on adult critically ill patients with ICU sleep deprivation: a study protocol and statistical analysis plan for a randomized controlled trial

Background: Sleep deprivation is common in critically ill patients in intensive care unit (ICU). It can result in delirium, difficult weaning, repeated nosocomial infections, prolonged ICU length of stay and increased ICU mortality. Melatonin, a physiological sleep regulator, is well known to benefit sleep quality of certain people, but evidence for effectiveness in ICU sleep disturbance is still limited. Methods/design: The study is a prospective, randomized, double-blind, controlled, parallel-group design. Eligible patients are randomly assigned to one of the two treatment study groups, labeled ‘Melatonin group’ or ‘Placebo group’. Oral melatonin 3 mg or placebo is administered at 21:00 p.m. on four consecutive days. Earplugs and eye masks are made available for use of every participant. We plan to enroll 164 patients. The primary outcome is the objective sleep quality measured by the 24-hour polysomnography. The secondary outcomes are subjective sleep quality assessed by the Richards Campbell Sleep Questionnaire, anxiety level evaluated by the Visual Analogue Scale-Anxiety, delirium-free days in 8 days and 28 days, ventilation-free days in 28 days, antibiotic-free days, ICU length of stay, over all ICU mortality in 28 days and the incidence and severity of side effects of melatonin in ICU patients. Additionally, the body stress levels, oxidative stress level and inflammation level are obtained via measuring plasma melatonin, cortisone, norepinephrine, MDA, SOD, IL-6 and IL-8 concentration. Discussion: The proposed study will be the first randomized controlled study to use the polysomnography, which is a gold standard of assessing sleep quality to evaluate the effect of melatonin on the sleep quality and circadian rhythms of ICU patients. The results may provide a new treatment for ICU patients with sleep deprivation that is safe, effective and easily implementable in daily practice. Trial registration: ClinicalTrials (NCT): ChiCTR-TRC-4004319.