Prevention of Delirium in Intensive Care by Melatonin

Treatment of the study is a single daily fixed-hour (21h) dose of 15 mL of an oral syrup, at one of the 3 following concentrations of melatonin: 0 mg/ml i.e. 0 mg/day (placebo); 0.02 mg/ml, i.e. 0.3 mg/day (low dose of melatonin) or 0.2 mg/ml, i.e. 3 mg/day (high dose of melatonin). The three dosages will be identical in appearance and volume.Treatment will be administered up to Day-14 (or death or discharge if these occur before Day-14). Randomization will be stratified by center.

Inclusion criteria

• Age ≥18 years
• Patient under invasive mechanical ventilation
• Anticipated stay in intensive care unit of at least 48 hours
• Informed consent signed by the patient or a relative or emergency consent

Exclusion criteria

• Invasive mechanical ventilation for more than 48 hours
• known pregnancy or breastfeeding
• No understanding of the French language, deafness
• Dementia (Mini Mental State <20) or known chronic psychosis
• Delirium (positive CAM-ICU score) before or at the time of randomization
• Alcohol withdrawal syndrome before or at the time of randomization with Cushman score ≥5
• Inability to use the enteral route, food intolerance with vomiting
• Severe hepatic insufficiency (prothrombin level <30%)
• Ongoing treatment with melatonin or a drug that interacts or modifies its metabolism (fluvoxamine, 5- or 8-methoxypsoralen, estrogen, cimetidine, carbamazepine, rifampicin)
• known allergy to melatonin
• moribund state
• Patient admitted to intensive care for cardiopulmonary arrest, stroke, head trauma, neurosurgery.
• Patient not affiliated to social security
• Patient participating in another interventional clinical study with melatonin and / or for whom delirium is the primary endpoint