Simvastatin in the acute respiratory distress syndrome
P : ARDS, adults
Patients were eligible if they were intubated and mechanically ventilated and were within 48 hours after the onset of ARDS as defined by a ratio of the partial pressure of arterial oxygen (PaO) to the fraction of inspired oxygen (FiO) of 300 mm Hg or less, if bilateral pulmonary infiltrates consistent with pulmonary edema were present on chest radiography, and if there was no evidence of left atrial hypertension.
E : once-daily simvastatin (at a dose of 80 mg) , n=259
C : placebo tablets, n=281
O : There was no significant difference between the study groups in the mean (±SD) number of ventilator-free days (12.6±9.9 with simvastatin and 11.5±10.4 with placebo, P=0.21)
There was no significant difference between the two groups in the incidence of serious adverse events related to the study drug.
T : multicenter, double-blind, RCT
Sample-size assumptions were based on previously published data.Assuming a mean (±SD) number of ventilator-free days of 12.7±10.6, we estimated that a sample of 524 patients would need to be enrolled in order for the study to have 80% power, at a two-tailed significance level of 0.05, to detect a mean between-group difference of 2.6 ventilator-free days. On the basis of data from the Pulmonary Artery Catheters in Management of Patients in Intensive Care (PAC-Man) trial, we estimated that the study-withdrawal rate would be 3%, and we therefore calculated that the study required a total of 540 patients.