6/28/23, 11:22 PM Nishikimi Pathway Feedback Search Clinical Topics Home Studies Nishikimi Nishikimi Trial question What is the effect of ramelteon, a melatonin agonist, among critically ill patients in the ICU? Study design Single center Double blinded RCT Population Characteristics of study participants 35.0% female N = 88 65.0% male 88 patients (31 female, 57 male) Inclusion criteria: patients in the ICU who could take medicines PO or through a nasogastric tube during the first 48 hours of admission Key exclusion criteria: already in receipt of ramelteon or fluvoxamine maleate prior to the admission, known allergy to ramelteon, refusal to provide consent for participation in the study Interventions N=45 ramelteon (8 mg/day at 20:00 hours every day until discharge from the ICU) N=43 placebo (1 g/day of lactose powder at 20:00 hours every day until discharge from the ICU) Primary outcome Duration of intensive care unit stay 5.9 days 5.86 4.56 4.4 days 2.9 days 1.5 days Significant decrease https://web.pathway.md/studies/recRp0GetpPY9oBtU 1/2 6/28/23, 11:22 PM Nishikimi Pathway 0.0 days Ramelteon Placebo Significant decrease in duration of ICU stay (4.56 days vs. 5.86 days; AD -1.3 days, 95% CI -2.46 to -0.14) Secondary outcomes Significant increase in occurrence rate of delirium (24.4% vs. 46.5%; OR 2.69, 95% CI 1.09 to 6.65) Significant decrease in duration of delirium (0.78 days vs. 1.4 days; AD -0.62 days, 95% CI -1.24 to 0) No significant difference in death at discharge (6.7% vs. 7.5%; RR 0.89, 95% CI -1273.77 to 1275.55) Safety outcomes No significant difference in mean hours of sleep. Significant differences in awakenings per night (0.80 times per night vs. 1.31 times per night), nights without awakenings (51% vs. 30%). Conclusion In patients in the ICU who could take medicines PO or through a nasogastric tube during the first 48 hours of admission, ramelteon was superior to placebo with respect to duration of ICU stay. Reference Mitsuaki Nishikimi, Atsushi Numaguchi, Kunihiko Takahashi et al. Effect of Administration of Ramelteon, a Melatonin Receptor Agonist, on the Duration of Stay in the ICU: A Single-Center Randomized Placebo-Controlled Trial. Crit Care Med. 2018 Jul;46(7):1099-1105. Open reference URL https://web.pathway.md/studies/recRp0GetpPY9oBtU 2/2