Acute lung injury (ALI)
Conditions
Interventions
Trade Name: simvastatin 40mg
Product Name: simvastatin 40mg
Pharmaceutical Form: Coated tablet
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Gastroenteral use
Sponsors
Belfast City Hospital Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Healthy non-smoking subjects 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) 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, alcohol abuse or abnormal liver function tests: transaminases > 3 times upper limit normal range • renal impairment (calculated creatinine clearance less than 60mL/minute) • known lactose intolerance • history of asthma • participation in other trials within 30 days • pregnancy, breast-feeding or women of childbearing potential not using adequate contraception; • 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 for 4 days will reduce pulmonary inflammation induced by LPS inhalation in humans. The primary outcome measure will be a reduction in bronchoalveolar lavage (BAL) CXCL8 concentration between the simvastatin and placebo treated groups. ;Secondary Objective: The secondary aims are to investigate if treatment with simvastatin will modulate: 1) alveolar inflammatory response 2) plasma inflammatory response 3) alveolar matrix metalloproteinase activity 4) intracellular signalling in the alveolar space 5) indices of alveolar epithelial and endothelial function and injury to determine the potential mechanisms by which simvastatin may be beneficial in ALI. The risk of adverse effects of simvastatin is dose dependent but on the basis of current evidence it is unknown if lower doses of simvastatin attenuate the mechanisms important in the development of lung injury. A pilot study of simvastatin 80mg in the treatment of ALI/ARDS is currently ongoing (EudraCT number: 2006-001414-33). If a beneficial effect was confirmed, a large phase 3 clinical trial to determine effectiveness and safety of simvastatin in patients with ALI/ARDS would be required. This current study would inform the rationale for the dose of simvastatin to be used. ;Primary end point(s): The primary outcome measure will be a reduction in BAL CXCL8 concentration between the simvastatin and placebo treated groups. | — |
Countries
United Kingdom
Outcome results
None listed