双醋瑞因与安慰剂治疗膝关节伴渗出性滑膜炎骨关节炎的随机对照试验研究方案(DICKENS)。
Study protocol for a randomised controlled trial of diacerein versus placebo to treat knee osteoarthritis with effusion-synovitis (DICKENS).
机构信息
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
出版信息
Trials. 2022 Sep 11;23(1):768. doi: 10.1186/s13063-022-06715-w.
BACKGROUND
There is an unmet need for treatments for knee osteoarthritis (OA). Effusion-synovitis is a common inflammatory phenotype of knee OA and predicts knee pain and structural degradation. Anti-inflammatory therapies, such as diacerein, may be effective for this phenotype. While diacerein is recommended for alleviating pain in OA patients, evidence for its effectiveness is inconsistent, possibly because studies have not targeted patients with an inflammatory phenotype. Therefore, we will conduct a multi-centre, randomised, placebo-controlled double-blind trial to determine the effect of diacerein on changes in knee pain and effusion-synovitis over 24 weeks in patients with knee OA and magnetic resonance imaging (MRI)-defined effusion-synovitis.
METHODS
We will recruit 260 patients with clinical knee OA, significant knee pain, and MRI-detected effusion-synovitis in Hobart, Melbourne, Adelaide, and Perth, Australia. They will be randomly allocated to receive either diacerein (50mg twice daily) or identical placebo for 24 weeks. MRI of the study knee will be performed at screening and after 24 weeks of intervention. The primary outcome is improvement in knee pain at 24 weeks as assessed by a 100-mm visual analogue scale (VAS). Secondary outcomes include improvement in volumetric (ml) and semi-quantitative (Whole-Organ Magnetic Resonance Imaging Score, 0-3) measurements of effusion-synovitis using MRI over 24 weeks, and improvement in knee pain (VAS) at 4, 8, 12, 16, and 20 weeks. Intention-to-treat analyses of primary and secondary outcomes will be performed as the primary analyses. Per protocol analyses will be performed as the secondary analyses.
DISCUSSION
This study will provide high-quality evidence to determine whether diacerein improves pain, changes disease trajectory, and slows disease progression in OA patients with effusion-synovitis. If diacerein proves effective, this has the potential to significantly benefit the substantial proportion (up to 60%) of knee OA patients with an inflammatory phenotype.
TRIAL REGISTRATION
Australian and New Zealand Clinical Trial Registry ACTRN12618001656224 . Registered on 08 October 2018.
背景
膝骨关节炎（OA）的治疗存在未满足的需求。渗出性滑膜炎是膝 OA 的一种常见炎症表型，可预测膝关节疼痛和结构退化。抗炎疗法，如双醋瑞因，可能对此表型有效。虽然双醋瑞因被推荐用于缓解 OA 患者的疼痛，但证据并不一致，这可能是因为研究并未针对炎症表型的患者。因此，我们将进行一项多中心、随机、安慰剂对照、双盲试验，以确定双醋瑞因对 24 周内膝骨关节炎患者膝关节疼痛和渗出性滑膜炎变化的影响，这些患者的膝关节有 MRI 定义的渗出性滑膜炎。
方法
我们将在澳大利亚的霍巴特、墨尔本、阿德莱德和珀斯招募 260 名有临床膝关节 OA、明显膝关节疼痛和 MRI 检测到的渗出性滑膜炎的患者。他们将被随机分配接受双醋瑞因（50mg，每日 2 次）或相同的安慰剂治疗 24 周。在筛选和干预 24 周后，将对研究膝关节进行 MRI 检查。主要结局是通过 100mm 视觉模拟量表（VAS）评估的 24 周时膝关节疼痛的改善。次要结局包括 24 周内 MRI 评估的渗出性滑膜炎的容积（ml）和半定量（全器官磁共振成像评分，0-3）测量的改善，以及 4、8、12、16 和 20 周时膝关节疼痛（VAS）的改善。主要和次要结局的意向治疗分析将作为主要分析进行。方案分析将作为次要分析进行。
讨论
这项研究将提供高质量的证据，以确定双醋瑞因是否能改善有渗出性滑膜炎的 OA 患者的疼痛、改变疾病轨迹和减缓疾病进展。如果双醋瑞因有效，这有可能使相当比例（高达 60%）的炎症表型膝骨关节炎患者显著受益。
试验注册
澳大利亚和新西兰临床试验注册中心 ACTRN12618001656224。于 2018 年 10 月 8 日注册。
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