Clinical Trials

Inclusion Criteria

• Systemic inflammatory response syndrome defined as meeting criteria for a systemic inflammatory response
  • White blood cell count >12,000 or <4,000 or >10% band forms
  • Body temperature >38 degrees Celsius (C) (any route) or <36 degrees C (accepting core temperatures only such as indwelling catheter, esophageal, rectal)
• Heart rate (> 90 beats/min) or receiving medications that slow heart rate or paced rhythm
• Suspected or proven infection of the thorax, urinary tract, abdomen, skin, sinuses, central venous catheters, or bacterial meningitis
• ALI as defined by acute onset of
  • PaO2 / FiO2 ≤ 300 intubated
  • If altitude > 1000m, then PaO2 / FiO2 ≤ 300 x (PB/760)
  • Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph
  • Requirement for positive pressure ventilation via an endotracheal tube
  • No clinical evidence of left atrial hypertension, or if measured, a Pulmonary Arterial Wedge Pressure (PAOP) less than or equal to 18 mm Hg
    • If a patient has a PAOP > 18 mmHg, then the other criteria must persist for more than 12 hours after the PAOP has declined to ≤ 18 mmHg, and still be within the 48-hour enrollment window
    • "Acute onset" is defined as the duration of the hypoxemia and the chest radiograph criteria must be ≤ 28 days at the time of randomization
    • Opacities considered "consistent with pulmonary edema" include any patchy or diffuse opacities not fully explained by mass, atelectasis, or effusion or opacities known to be chronic (> 28 days)
    • The findings of vascular redistribution, indistinct vessels, and indistinct cardiac borders are not considered "consistent with pulmonary edema"
• All ALI criteria must occur within the same 24 hour period
  • The onset of ALI is when the last ALI criterion is met
  • Must be enrolled within 48 hours of ALI onset and no more than 7 days from the initiation of mechanical ventilation
• SIRS criteria must occur within the 72 hours before or the 24 hours after ALI onset
• Information for determining when these time window criteria were met may come from either the Network hospital or a referring hospital reports

Exclusion Criteria

• No consent and unable to obtain consent
• Age less than 18 years
• More than 7 days since initiation of mechanical ventilation
• More than 48 hours since meeting ALI inclusion criteria
• Patient, surrogate, or physician not committed to full support
• Unable to receive or unlikely to absorb enteral study drug
• Rosuvastatin specific exclusions
  • Receiving a statin medication within 48 hours of randomization
  • Allergy or intolerance to statins
  • Physician insistence for the use or avoidance of statins during the current hospitalization
  • Creatine Kinase (CK) , alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper limit of normal
  • Diagnosis of hypothyroidism and not on thyroid replacement therapy
  • Pregnancy or breast feeding
  • Receiving niacin, fenofibrate or cyclosporine, gemfibrozil, atazanavir, lopinavir, ritonavir, daptomycin
• Severe chronic liver disease
• Moribund patient not expected to survive 24 hours
• Chronic respiratory failure defined as PaCO2 > 60 mm Hg in the outpatient setting
• Home mechanical ventilation (noninvasive ventilation or via tracheotomy) except for CPAP/BIPAP (Continuous Positive Airway Pressure/BiLevel Positive Airway Pressure) used solely for sleep-disordered breathing
• Diffuse alveolar hemorrhage from vasculitis
• Burns > 40% total body surface
• Interstitial lung disease of severity sufficient to require continuous home oxygen therapy
• Unwillingness or inability to utilize the ARDS network 6 ml/kg Predicted Body Weight (PBW) ventilation protocol
• Cardiac disease classified as NYHA (New York Heart Association) class IV
• Myocardial infarction within past 6 months
• Intraparenchymal Central Nervous System (CNS) bleed within a month of randomization
• Temperature >40.3 C in the 6 hours before randomization