Melatonin for prevention of delirium in patients receiving mechanical ventilation in the intensive care unit: a multiarm multistage adaptive randomized controlled clinical trial (DEMEL)
Abstract
To determine the dose of melatonin with an optimal pharmacokinetic profile and to test whether this dose reduces the prevalence of delirium in mechanically ventilated ICU patients as compared to placebo. DEMEL, a multicenter adaptive phase 2b/3 randomized, placebo-controlled, double-blind trial included patients at 20 health centers in France from February 1st, 2019 through January 5th, 2021. Patients were randomized (1:1:1) to receive either placebo or low (0.3 mg) or high (3 mg) dose melatonin enterally at 9:00 p.m. for 14 consecutive nights or until death or ICU discharge, whichever came first. The interim primary endpoint (activity stage) was the percentage of patients who achieved an optimal melatonin pharmacokinetic profile 24 h after starting study treatment; the final primary endpoint (efficacy phase) was the percentage of patients who experienced delirium between randomization and day 14 (or until death or ICU discharge, whichever came first). Delirium was assessed twice daily using the Confusion Assessment Method for ICU. We randomized 355 patients and included 334 in the primary analysis. At the preplanned analysis of the activity stage performed in 75 patients, the low-dose melatonin group had the highest rate of optimal pharmacokinetic profiles (12/24, 50%) when compared with the high-dose melatonin group (6/25, 24%) and the placebo group (0/26). Therefore, the Steering Committee recommended that the high-dose melatonin group be discontinued and that the…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 355 participants or records.
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