他汀类药物的使用对症状性膝骨关节炎是否具有疾病修饰作用？一项随机对照试验的研究方案。
Does statin use have a disease modifying effect in symptomatic knee osteoarthritis? Study protocol for a randomised controlled trial.
机构信息
Department of Epidemiology and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, 3004, Australia.
Menzies Institute for Medical Research, University of Tasmania, Private Bag 23, Hobart, TAS, 7000, Australia.
出版信息
Trials. 2015 Dec 23;16:584. doi: 10.1186/s13063-015-1122-2.
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.
TRIAL REGISTRATION
Australian New Zealand Clinical Trials Registry: ACTRN12613000190707 , registered on 18 February 2013.
背景
骨关节炎（OA）是一个主要的临床和公共卫生问题，目前没有被批准具有疾病修饰作用的药物。羟甲基戊二酰辅酶 A 还原酶抑制剂，即“他汀类药物”，是一种广泛用于预防心血管事件的药物类别，通过多种机制可能影响 OA 的进展，包括其对脂代谢和炎症的影响。这项多中心、随机、双盲、安慰剂对照试验的目的是确定阿托伐他汀是否能在 2 年内减少有症状的膝骨关节炎患者的膝关节结构变化和症状进展。
方法/设计：350 名有症状的膝骨关节炎患者将通过骨关节炎临床试验网络（在墨尔本、霍巴特和阿德莱德）招募。他们将被随机分配到研究的两个组，每天接受 40 毫克阿托伐他汀或相同的安慰剂治疗 2 年。在基线和 2 年后将对膝关节进行磁共振成像检查。将使用经过验证的方法评估膝关节结构、症状和功能。主要结局是膝关节软骨体积的年变化百分比。次要结局包括软骨缺损、骨髓病变、膝关节疼痛和功能的进展。主要分析将按意向治疗进行，但也将进行方案分析。
讨论
该研究将提供高质量的证据，以确定阿托伐他汀是否通过延迟膝骨关节炎的结构和症状进展，对 OA 具有新的疾病修饰作用。因此，该试验具有重大的公共卫生和临床意义，因为如果发现阿托伐他汀有益，它可以通过延迟和可能减少关节置换手术的需求来产生大量的成本节约，并为 OA 患者提供显著的生活质量改善。
试验注册
澳大利亚新西兰临床试验注册中心：ACTRN12613000190707，于 2013 年 2 月 18 日注册。
Zotero 插件