A protocol for a multicentre, randomised, double-blind, placebo-controlled trial to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change and knee pain over 24 months in knee osteoarthritis patients - ZAP2.
A protocol for a multicentre, randomised, double-blind, placebo-controlled trial to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change and knee pain over 24 months in knee osteoarthritis patients - ZAP2.
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DOI：
10.1186/s12891-018-2143-2
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发表时间：
2018-07-18
影响因子：
2.3
通讯作者：
Jones G
中科院分区：
文献类型：
--
作者：
Aitken D;Laslett LL;Cai G;Hill C;March L;Wluka AE;Wang Y;Blizzard L;Cicuttini F;Jones G
双膦酸盐是一类减缓骨质流失的药物，是治疗膝骨关节炎（OA）患者的有希望的候选药物。在一项初步研究中，我们证明了唑来膦酸在6个月的时间里减轻了伴有明显膝关节疼痛和骨髓损伤的膝OA患者的膝关节疼痛和软骨下骨髓病变（BMLs）的大小。随着时间的推移，BML大小的减少是否会转化为软骨损失的减少，需要一个更长、更大的研究来评估。我们目前正在进行一项为期24个月的多中心、随机、双盲、安慰剂对照试验，旨在比较每年注射唑来膦酸和安慰剂对膝关节炎患者膝关节结构改变（使用磁共振成像（MRI）评估）和膝关节疼痛的影响。将在霍巴特、墨尔本、悉尼和阿德莱德招募264名临床膝关节OA、明显膝关节疼痛和MRI显示的软骨下脑损伤患者。他们将被随机分配到研究的两组，在基线和1年后，每年接受相同的静脉输注100毫升含唑来膦酸（5毫克/100毫升）或安慰剂（0.9% NaCl 100毫升）的液体。在筛查、第6个月和第24个月对研究膝关节进行MRI检查。膝关节结构、症状和功能将使用有效的方法进行评估。主要结果是胫骨股骨软骨体积（mm3）在24个月内的绝对变化。次要结局包括3个月、6个月、12个月、18个月和24个月的膝关节疼痛改善，6个月和24个月的BML大小减少。主要分析将是主要和次要结局的意向治疗分析。每个协议分析将作为二次分析执行。本研究将提供高质量的证据来评估唑来膦酸是否通过减缓软骨丢失和减轻疼痛而在OA中具有新的疾病改善作用。如果唑来膦酸被证明是有效的，它表明通过延迟或减少关节置换手术的需要来节省巨大的成本潜力，并有可能极大地改善OA患者的生活质量。澳大利亚新西兰临床试验注册：ACTRN12613000039785，注册于2013年1月14日。
Bisphosphonates are a class of drugs that slow bone loss and are a promising candidate to treat knee osteoarthritis (OA) patients. In a pilot study, we demonstrated that zoledronic acid reduced knee pain and size of subchondral bone marrow lesions (BMLs) over 6 months in knee OA patients with significant knee pain and BMLs. A longer, larger study is required to assess whether decreases in BML size will translate to reductions in cartilage loss over time. We are currently conducting a multicentre, randomised, double-blind, placebo-controlled trial over 24 months that aims to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change (assessed using magnetic resonance imaging (MRI)) and knee pain in knee OA patients. Two hundred sixty-four patients with clinical knee OA, significant knee pain and subchondral BMLs present on MRI will be recruited in Hobart, Melbourne, Sydney and Adelaide. They will be randomly allocated to the two arms of the study, receiving an annual identical intravenous infusion of either 100 mL of fluid containing zoledronic acid (5 mg/100 mL) or placebo (0.9% NaCl 100 mL), at baseline and 1 year later. MRI of the study knee will be performed at screening, month 6 and 24. Knee structure, symptoms and function will be assessed using validated methods. The primary outcome is absolute change in tibiofemoral cartilage volume (mm3) over 24 months. Secondary outcomes include improvement in knee pain over 3, 6, 12, 18, and 24 months and reductions in BML size over 6 and 24 months. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per protocol analyses will be performed as the secondary analyses. This study will provide high-quality evidence to assess whether zoledronic acid has a novel disease modifying effect in OA by slowing cartilage loss and reducing pain. If zoledronic acid proves effective, it suggests great potential for cost savings through a delay or reduced need for joint replacement surgery, and potential for great improvements in quality of life for OA suffers. Australian New Zealand Clinical Trials Registry: ACTRN12613000039785, registered on 14 January 2013.
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影响因子：
1.9
作者：
Baroja-Mazo A;Pelegrín P
通讯作者：
Pelegrín P
影响因子：
--
作者：
Hunter, David J.;Zhang, Yuqing;Felson, David T.
通讯作者：
Felson, David T.
影响因子：
6.2
作者：
Cauley, Jane A.;Black, Dennis;Reid, Ian R.
通讯作者：
Reid, Ian R.
影响因子：
27.4
作者：
Dore, Dawn A.;Winzenberg, Tania Maree;Jones, Graeme
通讯作者：
Jones, Graeme
影响因子：
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作者：
Felson, David T.;Niu, Jingbo;Aliabadi, Piran
通讯作者：
Aliabadi, Piran