Statins for Acutely Injured Lungs From Sepsis

• Status: Terminated
• Trial end date: 2013-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Rosuvastatin Calcium

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