藏族药如意珍宝丸治疗膝骨关节炎的多中心、随机、双盲、安慰剂、平行对照临床试验

A Multicenter， Randomized， Double-blind， and Placebo-parallel Controlled Trial of Tibetan Medicine Ruyi Zhenbaowan in Treatment of Knee Osteoarthritis

摘要:

目的 通过前瞻性的多中心、随机、双盲、安慰剂、平行对照临床试验，评价藏族药如意珍宝丸治疗初、早期膝骨关节炎（KOA）的临床疗效。方法 2021年10月13日至2021年12月25日期间于中国中医科学院望京医院等15个分中心共纳入符合纳排标准的KOA受试者240例，随机分为观察组与对照组，每组各120例。观察组受试者的干预措施为如意珍宝丸+健康宣教，对照组受试者的干预措施为如意珍宝丸安慰剂+健康宣教。两组受试者的干预周期均为4周，结束干预后随访4周。主要结局指标为西安大略和麦克马斯特大学骨关节炎指数评分（WOMAC评分）总积分，次要结局指标为视觉模拟（VAS）疼痛评分的应答率、WOMAC子项目积分（关节疼痛、关节僵硬、关节功能）、生活质量（SF-12）评分、中医证候评分。结果 （1）疗效评价。边际模型结果显示，如意珍宝丸治疗膝骨关节炎改善WOMAC总分、WOMAC疼痛评分方面，观察组优于对照组，差异具有统计学意义（P<0.05）。两组在改善VAS评分应答率、WOMAC功能评分、WOMAC僵硬评分、生活质量-躯体健康（SF12-PCS）评分、生活质量-精神健康（SF12-MCS）评分、中医证候评分方面，差异无统计学意义。（2）亚组分析。①在VAS评分应答率方面，基线VAS评分为（4，5］的受试者，观察组应答率高于对照组，差异具有统计学意义（P<0.05）。②在中医证候评分方面，年龄段在［56，60］岁、［61，65］岁的受试者，观察组中医证候总分的降幅优于对照组，差异具有统计学意义（P<0.05）。结论 藏族药如意珍宝丸对KOA初、早期轻型患者，在改善WOMAC总分、VAS评分应答率、WOMAC疼痛评分、WOMAC功能评分、中医证候评分方面具有较好的临床疗效，可以填补藏族药如意珍宝丸治疗KOA循证证据的不足，为民族医药的传承与发展做出了示范研究。

Abstract:

Objective This study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial.Method From October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score.Result （1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）.Conclusion Tibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.