6/28/23, 11:19 PM MoDUS Pathway Feedback Search Clinical Topics Home Studies MoDUS MoDUS Disease ICU delirium Trial question What is the effect of early administration of simvastatin in critically ill patients with delirium undergoing mechanical ventilation? Study design Single center Double blinded RCT Population Characteristics of study participants 42.0% female N = 142 58.0% male 142 patients (60 female, 82 male) Inclusion criteria: critically ill patients needing mechanical ventilation within 72 h of ICU admission Key exclusion criteria: age < 18 years; pregnant or breastfeeding; known allergy to statins; CK concentration > 10 times the ULN range; ALT concentration > 8 times the ULN range Interventions N=71 simvastatin (80 mg by enteral administration daily for up to a maximum of 28 days) N=71 placebo (matching placebo by enteral administration daily for up to a maximum of 28 days) Primary outcome Days alive without delirium and coma at 14 days https://web.pathway.md/studies/recUEDnwOdcsYrfIg 1/2 6/28/23, 11:19 PM MoDUS Pathway 6.1 days 6.1 5.7 4.6 days 3.0 days 1.5 days No significant difference 0.0 days Simvastatin Placebo No significant difference in days alive without delirium and coma at 14 days (5.7 days vs. 6.1 days; AD -0.4 days, 95% CI -1.3 to 2.1) Secondary outcomes No significant difference in ventilator-free days at 28 days (13.7 days vs. 15.5 days; AD -1.8 days, 95% CI -2.1 to 5.6) No significant difference in organ failure-free days at 28 days (14.3 days vs. 15.7 days; AD -1.5 days, 95% CI -2.4 to 5.3) No significant difference in length of hospital stay until death or discharge (20.3 days vs. 20.4 days; AD -0.2 days, 95% CI -6.3 to 6.7) Safety outcomes No significant differences in death from all causes at 6 months, increase in alanine transaminase to > eight times the upper limit or normal. Significant difference in percentage of patients with creatinine kinase concentration > ten times the ULN (11% vs. 4%). Conclusion In critically ill patients needing mechanical ventilation within 72 h of ICU admission, simvastatin was not superior to placebo with respect to days alive without delirium and coma at 14 days. Reference Valerie J Page, Annalisa Casarin, E Wesley Ely et al. Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MoDUS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2017 Sep;5(9):727-737. Open reference URL https://web.pathway.md/studies/recUEDnwOdcsYrfIg 2/2