Acute lung injury (ALI)
Conditions
Interventions
Trade Name: simvastatin 40mg
Product Name: simvastatin 40mg
Pharmaceutical Form: Coated tablet
Pharmaceutical form of the placebo: Capsule*
Sponsors
The Royal Group Hospitals Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Adult patients undergoing oesophagectomy for oesophageal cancer at the Royal Victoria Hospital, Belfast (RVH) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • age 5 times upper limit normal range • known active liver disease (Child’s Pugh score > 11), or abnormal liver function tests: transaminases > 3 times upper limit normal range • renal impairment (calculated creatinine clearance less than 30mL/minute) • inability to take oral medication pre-operatively • known lactose intolerance • participation in other intervention trials within 30 days • pregnancy, breast-feeding or women of childbearing potential not using adequate contraception; • patients taking corticosteroids or non-steroidal anti-inflammatory drugs • current treatment with statins • known hypersensitivity to the study medication • a previous adverse reaction to statins • concomitant use of fibrates or other lipid-lowering therapy • concomitant use of itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, grapefruit juice, cyclosporine, danazol, amiodarone, verapamil or diltiazem. • consent declined
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The hypothesis of the study is that treatment with simvastatin can prevent lung injury and inflammation in humans undergoing oesophagectomy as assessed by important surrogate clinical outcomes. The primary outcome is to evaluate the efficacy of simvastatin to improve pulmonary vascular function between the simvastatin and placebo treated groups ; Secondary Objective: The following secondary outcomes will also be assessed: 1) Oxygenation assessed by the PaO2: FiO2 ratio 2) Respiratory system compliance 3) Safety and tolerability The secondary aims are to investigate if treatment with simvastatin will modulate: 1) biomarkers of alveolar epithelial and endothelial function and injury 2) plasma and pulmonary cytokine response 3) systemic and pulmonary inflammation and oxidative stress to determine the potential mechanisms by which simvastatin may be beneficial in ALI. ; Primary end point(s): The primary outcome measure will be pulmonary vascular function as measured by pulmonary dead space fraction (Vd/Vt) at 6 hours following one lung ventilation or prior to extubation if earlier between the simvastatin and placebo treated groups This endpoint was chosen as dysregulated alveolar inflammation causes pulmonary vascular endothelial injury, important in the development of ALI/ARDS. In addition, elevated Vd/Vt is predictive of mortality in ALI/ARDS. The 6 hour time point was chosen as markers of inflammation and oxidative stress can be detected at this time. | — |
Countries
United Kingdom
Outcome results
None listed