MoDUS
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
58.0% male
N = 142
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; pregnancy or lactation; 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
5.7 days
6.1 days
6.1 days
4.6 days
3.0 days
1.5 days
0.0 days
Simvastatin
Placebo
No significant
difference ↔
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 all-cause mortality at 6 months, increase in alanine transaminase to > eight times the upper limit or normal.
Significant difference in 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.
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