Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) Respiratory Acute lung injury and acute respiratory distress syndrome (ARDS)
Conditions
Interventions
Patients will be stratified for the presence of severe sepsis as a clinical risk factor for the development of acute lung injury. Stratified block randomisation using a microcomputer to simvastatin 80
Sponsors
The Royal Group Hospitals Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Mechanically ventilated adult patients admitted to the intensive care unit at the Royal Victoria Hospital, within 48 hours of the onset ALI or ARDS, will be eligible for inclusion in the study. ALI and ARDS will be defined according to the American European Consensus Conference definition.
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 17/04/2012 1. Age 10 times the upper limit of the normal range* 5. Transaminases >8 times the upper limit of the normal range* 6. Patients currently receiving ongoing and sustained treatment with any of the following; itraconazole, ketoconazole, HIV protease inhibitors, nefazodone, cyclosporine, amiodarone, verapamil or diltiazem. 7. Patients with severe renal impairment (estimated creatinine clearance less than 30ml/minute) not receiving renal replacement therapy 8. Severe liver disease (Child's Pugh score >12; Appendix 1) 9. Current or recent treatment (within 2 weeks) with statins 10. Physician decision that a statin is required for proven indication 11. Contraindication to enteral drug administration, e.g. patients with mechanical bowel obstruction. Patients with high gastric aspirates due to an ileus are not excluded. 12. Domiciliary mechanical ventilation except for CPAP/BIPAP used for sleep-disordered breathing. 13. Known participation in other investigational medicinal product (IMP) trials within 30 days 14. Consent declined 15. Treatment withdrawal imminent within 24 hours 16. Non-english speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available * If CK, ALT and AST values are not available as part of routine care, a blood sample will be obtained after informed consent but before randomisation. CK, ALT and AST values may be obtained up to 72 hours prior to randomisation. Previous exclusion criteria 1. Aged under 18 years 2. Pregnancy 3. Creatinine kinase (CK) more than five times upper limit of normal range 4. Transaminases more than three times upper limit of normal range 5. Participation in other intervention trials within previous 30 days 6. Current treatment with statins 7. Contraindication to enteral nutrition 8. Unlikely to survive beyond 48 hours 9. Patients with significant end stage disease as previously defined and assent declined from the next of kin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Reduction in extravascular lung water (EVLW) in the simvastatin treated group at day 7 | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measure (s) as of 17/04/2012 There are a number of secondary outcomes for this clinical trial which include clinical outcomes, safety, biological mechanisms and data for the economic evaluation. Clinical Outcomes 1. Change in oxygenation index (OI) from baseline to day 3, 7, 14 and 28 2. Change in sequential organ failure assessment (SOFA) score from baselines to days 3, 7, 14 and 28 3. Non pulmonary organ failure free days, (defined as the number of days in the first 28 days after randomisation that the patient has none of: cardiovascular support, renal support, liver support or neurological support). 4. All cause mortality 28 days post randomisation 5. Mortality at (first) discharge from critical care 6. Mortality at (first) discharge from hospital 7. Mortality at 12 months post randomisation Safety 8. CK >10 times the upper limit of normal (measured on days 1, 3, 7, 14, 21 and 28) 9. ALT/AST >8 times the upper limit of normal (measured on days 1, 3, 7, 14, 21 and 28) 10. Need for renal replacement therapy in patients with CK elevated >10 fold 11. Serious adverse events (SAEs) and occurrence of suspected unexpected serious adverse reactions (SUSARs). 12 Biological mechanisms 13 Health-related quality of life 14. Cost effectiveness Previous secondary outcome measure(s) 1. Physiological severity of lung injury as measured by PaO2:FiO2 ratio at day 7, respiratory compliance at day 7 2. Effects on the pulmonary circulation as measured by change in pulmonary dead space at day 7 3. Extra-pulmonary organ failure as measured by sequential organ failure assessment (SOFA) score at day 7 | — |
Countries
United Kingdom
Outcome results
None listed