Does statin use have a disease modifying effect in symptomatic knee osteoarthritis? Study protocol for a randomised controlled trial

Background: Osteoarthritis (OA) is a major clinical and public health problem, with no current medications approved as having disease modifying effects. HMG-CoA reductase inhibitors, or statins, a drug class widely used to prevent cardiovascular events, could potentially affect OA progression via a number of mechanisms including their effects on lipid metabolism and inflammation. The aim of this multicentre, randomised, double-blind, placebo-controlled trial is to determine whether atorvastatin reduces the progression of knee structural changes and symptoms over 2 years in patients with symptomatic knee OA. Methods/design: 350 patients with symptomatic knee OA will be recruited through the OA Clinical Trial Network (in Melbourne, Hobart and Adelaide). They will be randomly allocated to the two arms of the study, receiving either 40 mg of atorvastatin or identical placebo once daily for 2 years. Magnetic resonance imaging of the knee will be performed at baseline and 2 years later. Knee structure, symptoms and function will be assessed using validated methods. The primary outcome is annual percentage change in knee cartilage volume. Secondary outcomes include progression of cartilage defects, bone marrow lesions, knee pain and function. The primary analysis will be by intention to treat, but per protocol analyses will also be performed. Discussion: The study will provide high-quality evidence to address whether atorvastatin has a novel disease modifying effect in OA by delaying the structural and symptomatic progression of knee OA. Thus, the trial has major public health and clinical importance, as if found to be beneficial, atorvastatin could produce substantial cost savings by delaying and possibly reducing the need for joint replacement surgery, and provide marked improvements in quality of life for people with OA.