DEMEL
Trial question
What is the effect of melatonin in critically ill patients receiving mechanical ventilation?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
32.0% female
68.0% male
N = 301
301 patients (97 female, 204 male).
Inclusion criteria: adult critically ill patients receiving mechanical ventilation.
Key exclusion criteria: delirium onset before or at randomization; invasive mechanical ventilation > 48 hours prior to randomization; no enteral route available; pregnancy or lactation; hypersensitivity to melatonin; medications that interact with melatonin or modify its metabolism; hepatic impairment.
Interventions
N=147 melatonin (at a dose of 0.3 mg enterally for 14 consecutive nights).
N=154 placebo (matching placebo enterally).
Primary outcome
Delirium at day 14
54.4%
55.2%
55.2 %
41.4 %
27.6 %
13.8 %
0.0 %
Melatonin
Placebo
No significant
difference ↔
No significant difference in delirium at day 14 (54.4% vs. 55.2%; RR 0.99, 99% CI 0.8 to 1.21).
Secondary outcomes
No significant difference in delirium-free days at day 14 (3 days vs. 2 days; AD 1 days, 95% CI -1.25 to 3.25).
No significant difference in ventilator-free days at day 28 (16 days vs. 15 days; AD 1 days, 95% CI -13.4 to 15.4).
No significant difference in death in the ICU at day 28 (21.8% vs. 23.4%; RR 0.93, 95% CI -5.23 to 7.09).
Safety outcomes
No significant difference in adverse events.
Conclusion
In adult critically ill patients receiving mechanical ventilation, melatonin was not superior to placebo with respect to delirium at day 14.
Reference
Armand Mekontso Dessap, Jean-Damien Ricard, Damien Contou et al. Melatonin for prevention of delirium in patients receiving mechanical ventilation in the intensive care unit: a multiarm multistage adaptive randomized controlled clinical trial (DEMEL). Intensive Care Med. 2025 Jul 3. Online ahead of print.
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