Statins for Acutely Injured Lungs From Sepsis
Condition: Sepsis; Acute Lung Injury
MeSH terms: Sepsis; Toxemia; Lung Injury; Acute Lung Injury
Intervention: Rosuvastatin; Placebo
Intervention description: Subjects received an initial 40mg loading dose followed by 20 mg of study drug daily by mouth or feeding tube for 28 days or until discharged from the study hospital.; Subjects received placebo by mouth or feeding tube daily for 28 days or until discharged from study hospital.
Intervention MeSH terms: Rosuvastatin Calcium
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 745.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ALI; Sepsis; statin

Summary:

      Objective: assess the efficacy and safety of oral rosuvastatin in patients with
      sepsis-induced Acute Lung Injury (ALI).

      Hypothesis: Rosuvastatin therapy will improve mortality in patients with sepsis-induced ALI.
    

Eligibility criteria:

        Inclusion Criteria:

          -  1. Systemic inflammatory response syndrome (SIRS) defined as meeting at least criteria
             (a) or (b)for a systemic inflammatory response:

               1. White blood cell count >12,000 or <4,000 or >10% band forms

               2. Body temperature >38 degrees Celsius (C) (any route) or <36 degrees C (accepting
                  core temperatures only; indwelling catheter, esophageal, rectal)

               3. Heart rate (> 90 beats/min) or receiving medications that slow heart rate or
                  paced rhythm 2. Suspected or proven infection: Sites of infection include thorax,
                  urinary tract, abdomen, skin, sinuses, central venous catheters, and bacterial
                  meningitis (Appendix A).

                  3. ALI as defined by acute onset of:

               1. PaO2 / FiO2 ≤ 300 (intubated). If altitude > 1000m, then PaO2 / FiO2 ≤ 300 x
                  (PB/760), and

               2. Bilateral infiltrates consistent with pulmonary edema on frontal chest
                  radiograph, and

               3. Requirement for positive pressure ventilation via an endotracheal tube, and

               4. 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 follows: the duration of the hypoxemia criterion (#1) and the
        chest radiograph criterion (#2) 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 (3a-d above) must occur within the same 24 hour period. The onset of ALI
        is when the last ALI criterion is met. Patients 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:

          1. No consent/inability to obtain consent

          2. Age less than 18 years

          3. More than 7 days since initiation of mechanical ventilation

          4. More than 48 hours since meeting ALI inclusion criteria

          5. Patient, surrogate, or physician not committed to full support ).

          6. Unable to receive or unlikely to absorb enteral study drug

          7. 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

          8. Severe chronic liver disease

          9. Moribund patient not expected to survive 24 hours

         10. Chronic respiratory failure defined as PaCO2 > 60 mm Hg in the outpatient setting

         11. 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

         12. Diffuse alveolar hemorrhage from vasculitis

         13. Burns > 40% total body surface

         14. Interstitial lung disease of severity sufficient to require continuous home oxygen
             therapy

         15. Unwillingness or inability to utilize the ARDS network 6 ml/kg Predicted Body Weight
             (PBW) ventilation protocol

         16. Cardiac disease classified as NYHA (New York Heart Association) class IV

         17. Myocardial infarction within past 6 months

         18. Intraparenchymal Central Nervous System (CNS) bleed within a month of randomization.

         19. Temperature >40.3 C in the 6 hours before randomization