Objectives

The SAILS trial was intended to assess the efficacy and safety of oral rosuvastatin in patients with sepsis-induced Acute Lung Injury (ALI) and test the hypothesis that rosuvastatin therapy would improve the clinical outcomes of critically ill patients with sepsis-associated acute respiratory distress syndrome (ARDS).

Background

In ARDS, inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis.

Participants

Patients were eligible for enrollment if they were receiving positive-pressure mechanical ventilation through an endotracheal tube, had a ratio of the partial pressure of arterial oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of 300 or less, and had bilateral infiltrates on chest radiography that were consistent with pulmonary edema, without evidence of left atrial hypertension. Additionally, the subjects needed to meet at least one criterion for a systemic inflammatory response: a white blood cell count greater than 12,000 or less than 4,000 or at least 10% band forms, or a core body temperature of more than 38°C or less than 36°C.

Design

Patients were randomly assigned in permuted blocks to receive either enteral rosuvastatin or placebo. A 40 mg loading dose of the study drug was administered within four hours after randomization. Subsequently, maintenance doses of 20 mg were administered daily until the third day after discharge from the intensive care unit, study day 28, hospital discharge, or death, whichever came first. The primary outcome measure was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcome measures included the number of ventilator-free days to day 28, organ-failure-free days to day 14, and ICU-free days to day 28.

Conclusions

The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60 day in-hospital mortality or in mean ventilator-free days. The rosuvastatin group had fewer days free of hepatic or renal failure. Thus, rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction.

Additional Details

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