[1]郑昱新,葛继荣,刘文刚,等.痛宁凝胶外用治疗轻中度膝骨关节炎肾虚筋脉瘀滞证的随机、双盲、安慰剂对照、多中心临床研究[J].中医正骨,2022,34(06):17-24.
　ZHENG Yuxin,GE Jirong,LIU Wengang,et al.External application of Tongning(痛宁)gel for treatment of mild-to-moderate knee osteoarthritis with syndromes of kidney deficiency and tendon-vessel stasis:a randomized,double-blind,placebo-controlled,multicenter clinical study[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2022,34(06):17-24.
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痛宁凝胶外用治疗轻中度膝骨关节炎肾虚筋脉瘀滞证的随机、双盲、安慰剂对照、多中心临床研究()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第34卷
期数:
2022年06期
页码:
17-24
栏目:
临床研究
出版日期:
2022-06-20

文章信息/Info

Title:
External application of Tongning(痛宁)gel for treatment of mild-to-moderate knee osteoarthritis with syndromes of kidney deficiency and tendon-vessel stasis:a randomized,double-blind,placebo-controlled,multicenter clinical study
作者:
郑昱新; 葛继荣; 刘文刚; 杨俊兴; 何承建; 卢敏; 沈霖; 尹宏; 陈永强; 李智斌10; 孙庆; 谢利民; 詹红生
(1.上海中医药大学附属曙光医院,上海 201203; 2.福建省中医药研究院,福建 福州 350003; 3.广东省第二中医院,广东 广州 510095; 4.广州中医药大学第一附属医院,广东 广州 510405; 5.湖北省中医院,湖北 武汉 430061; 6.湖南中医药大学第一附属医院,湖南 长沙 410007; 7.华中科技大学同济医学院附属协和医院,湖北 武汉 430022; 8.南京市中医院,江苏 南京 210022; 9.上海市中医医院,上海 200071; 10.陕西中医药大学附属医院,陕西 咸阳 712000; 11.天津中医药大学第一附属医院,天津 300193; 12.中国中医科学院广安门医院,北京 100053)
Author(s):
ZHENG Yuxin; GE Jirong; LIU Wengang; YANG Junxing; HE Chengjian; LU Min; SHEN Lin; YIN Hong; CHEN Yongqiang; LI Zhibin; SUN Qing; XIE Limin; ZHAN Hongsheng
关键词:
骨关节炎; 膝;  痛宁凝胶;  临床试验
Keywords:
osteoarthritis; knee;  Tongning gel;  clinical trial
摘要:
目的:评价痛宁凝胶外用治疗轻中度膝骨关节炎肾虚筋脉瘀滞证的临床疗效和安全性。方法:采用随机、双盲、安慰剂对照、多中心临床试验,共纳入576例轻中度膝骨关节炎肾虚筋脉瘀滞证患者,痛宁凝胶组432例、安慰剂组144例。痛宁凝胶组于膝关节疼痛处外涂痛宁凝胶,安慰剂组于膝关节疼痛处外涂痛宁凝胶模拟剂; 2组均每日2次外涂皮肤,每次3 g,疗程3周。分别于治疗前及治疗开始后1周、2周、3周记录并比较2组患者的西安大略和麦克马斯特大学骨关节炎指数(Western Ontario and McMaster Universities osteoarthritis index,WOMAC)疼痛评分、僵硬评分、日常活动功能评分及总评分,于治疗开始后3周比较2组患者的综合疗效,观察并比较2组患者并发症发生情况。结果:①受试者退出情况。痛宁凝胶组1例患者因未按要求治疗而退出。②WOMAC疼痛评分。时间因素和分组因素存在交互效应(F=166.662,P=0.000); 2组患者WOMAC疼痛评分总体比较,差异有统计学意义,即存在分组效应(F=148.461,P=0.000); 治疗前后不同时间点之间WOMAC疼痛评分的差异有统计学意义,即存在时间效应(F=3.823,P=0.022); 2组患者WOMAC疼痛评分随时间延长均呈下降趋势,但2组的下降趋势不完全一致[(36.72±12.97)分,(31.93±12.22)分,(26.49±11.50)分,(20.29±11.79)分,F=148.461,P=0.000;(35.47±13.38)分,(33.44±13.11)分,(32.63±13.79)分,(31.61±15.00)分,F=8.574,P=0.000]; 治疗前及治疗开始后1周,2组患者的WOMAC疼痛评分比较,组间差异均无统计学意义(t=0.994,P=0.322; t=1.262,P=0.207); 治疗开始后2周、3周,痛宁凝胶组的WOMAC疼痛评分均低于安慰剂组(t=4.813,P=0.000; t=8.241,P=0.000)。③WOMAC僵硬评分。时间因素和分组因素存在交互效应(F=80.764,P=0.000); 2组患者WOMAC僵硬评分总体比较,差异有统计学意义,即存在分组效应(F=57.734,P=0.000); 治疗前后不同时间点之间WOMAC僵硬评分的差异无统计学意义,即不存在时间效应(F=1.920,P=0.148); 治疗前及治疗开始后1周,2组患者的WOMAC僵硬评分比较,组间差异均无统计学意义[(23.93±15.76)分,(23.38±16.24)分,t=0.362,P=0.717;(21.22±14.74)分,(22.00±15.93)分,t=0.530,P=0.594]; 治疗开始后2周、3周,痛宁凝胶组的WOMAC僵硬评分低于安慰剂组[(17.50±13.20)分,(20.95±15.75)分,t=2.374,P=0.019;(13.84±11.85)分,(20.21±15.87)分,t=5.103,P=0.000)。④WOMAC日常活动功能评分。时间因素和分组因素存在交互效应(F=159.442,P=0.000); 2组患者WOMAC日常活动功能评分总体比较,差异有统计学意义,即存在分组效应(F=145.611,P=0.000); 治疗前后不同时间点之间WOMAC日常活动功能评分的差异有统计学意义,即存在时间效应(F=7.790,P=0.000); 2组患者WOMAC日常活动功能评分随时间延长均呈下降趋势,但2组的下降趋势不完全一致[(34.11±11.51)分,(29.71±11.04)分,(24.42±10.37)分,(19.36±10.80)分,F=145.611,P=0.000;(32.65±11.94)分,(30.77±11.90)分,(29.66±12.46)分,(28.64±13.38)分,F=8.764,P=0.000]; 治疗前及治疗开始后1周,2组患者的WOMAC日常活动功能评分比较,组间差异均无统计学意义(t=1.310,P=0.191; t=0.983,P=0.328); 治疗开始后2周、3周,痛宁凝胶组的WOMAC日常活动功能评分均低于安慰剂组(t=4.554,P=0.000; t=7.542,P=0.000)。⑤WOMAC总评分。时间因素和分组因素存在交互效应(F=177.900,P=0.000); 2组患者WOMAC总评分总体比较,差异有统计学意义,即存在分组效应(F=150.622,P=0.000); 治疗前后不同时间点之间WOMAC总评分的差异有统计学意义,即存在时间效应(F=6.861,P=0.001); 2组患者WOMAC总评分随时间延长均呈下降趋势,但2组的下降趋势不完全一致[(33.81±11.34)分,(29.47±10.88)分,(24.27±10.26)分,(19.09±10.61)分,F=150.622,P=0.000;(32.46±11.72)分,(30.60±11.66)分,(29.55±12.23)分,(28.55±13.16)分,F=8.694,P=0.000]; 治疗前及治疗开始后1周,2组患者的WOMAC总评分比较,组间差异均无统计学意义(t=1.224,P=0.223; t=1.063,P=0.289); 治疗开始后2周、3周,痛宁凝胶组的WOMAC总评分均低于安慰剂组(t=4.662,P=0.000; t=7.820,P=0.000)。⑥综合疗效。治疗开始后3周,痛宁凝胶组临床控制29例、显效66例、有效248例、无效88例,安慰剂组临床控制2例、显效6例、有效14例、无效122例; 痛宁凝胶组的综合疗效优于安慰剂组(Z=12.310,P=0.000)。⑦依从性和安全性。除痛宁凝胶组1例患者退出外,其余患者依从性均较好,均按照医嘱完成治疗。痛宁凝胶组1例出现转氨酶轻度升高,1例出现局部皮肤轻度过敏; 安慰剂组4例出现局部皮肤轻度过敏; 均未做特殊处理,停药后转氨酶恢复正常,皮肤过敏自行消退。2组患者并发症发生率比较,差异无统计学意义(χ2=3.593,P=0.058)。结论:痛宁凝胶外用能减轻轻中度膝骨关节炎肾虚筋脉瘀滞证患者的膝关节疼痛和僵硬,改善患膝功能,且安全性较高。
Abstract:
Objective:To evaluate the clinical outcomes and safety of external application of Tongning(痛宁,TN)gel for treatment of mild-to-moderate knee osteoarthritis(KOA)with syndromes of kidney deficiency and tendon-vessel stasis.Methods:Five hundred and seventy-six mild-to-moderate KOA patients with kidney deficiency and tendon-vessel stasis syndromes were enrolled in the randomized,double-blind,placebo-controlled,multicenter clinical trial,432 cases in TN gel group and 144 cases in placebo group.The patients in TN gel group were treated with external application of TN gel at the pain spots of affected knee,while the ones in placebo group with external application of TN gel mimetic agent at the pain spots of affected knee.All patients in the 2 groups were treated twice a day,3 g at a time for consecutive 3 weeks.The Western Ontario and McMaster Universities osteoarthritis index(WOMAC)pain score,stiffness score,activity of daily living(ADL)function score and total score were recorded and compared between the 2 groups before the treatment and at 1,2 and 3 weeks after the beginning of the treatment respectively.Furthermore,the total outcomes were compared between the 2 groups at 3 weeks after the beginning of the treatment,and the complications were observed and compared between the 2 groups.Results:①One patient in TN gel group dropped out of the study for failing to be treated as required.②There was interaction between time factor and group factor in WOMAC pain score(F=166.662,P=0.000).There was statistical difference in WOMAC pain scores between the 2 groups in general,in other words,there was group effect(F=148.461,P=0.000).There was statistical difference in WOMAC pain scores between different timepoints before and after the treatment,in other words,there was time effect(F=3.823,P=0.022).The WOMAC pain scores presented a downward trend over time in the 2 groups,while the 2 groups were inconsistent with each other in the variation tendency(36.72±12.97,31.93±12.22,26.49±11.50,20.29±11.79 points,F=148.461,P=0.000; 35.47±13.38,33.44±13.11,32.63±13.79,31.61±15.00 points,F=8.574,P=0.000).There was no statistical difference in WOMAC pain scores between the 2 groups before the treatment and at 1 week after the beginning of the treatment(t=0.994,P=0.322; t=1.262,P=0.207),however,at 2 and 3 weeks after the beginning of the treatment,the WOMAC pain scores were lower in TN gel group compared to placebo group(t=4.813,P=0.000; t=8.241,P=0.000).③There was interaction between time factor and group factor in WOMAC stiffness score(F=80.764,P=0.000).There was statistical difference in WOMAC stiffness scores between the 2 groups in general,in other words,there was group effect(F=57.734,P=0.000).There was no statistical difference in WOMAC stiffness scores between different timepoints before and after the treatment,in other words,there was no time effect(F=1.920,P=0.148).There was no statistical difference in WOMAC stiffness scores between the 2 groups before the treatment and at 1 week after the beginning of the treatment(23.93±15.76 vs 23.38±16.24 points,t=0.362,P=0.717; 21.22±14.74 vs 22.00±15.93 points,t=0.530,P=0.594),however,at 2 and 3 weeks after the beginning of the treatment,the WOMAC stiffness scores were lower in TN gel group compared to placebo group(17.50±13.20 vs 20.95±15.75 points,t=2.374,P=0.019; 13.84±11.85 vs 20.21±15.87 points,t=5.103,P=0.000).④There was interaction between time factor and group factor in WOMAC ADL function score(F=159.442,P=0.000).There was statistical difference in WOMAC ADL function scores between the 2 groups in general,in other words,there was group effect(F=145.611,P=0.000).There was statistical difference in WOMAC ADL function scores between different timepoints before and after the treatment,in other words,there was time effect(F=7.790,P=0.000).The WOMAC ADL function scores presented a downward trend over time in the 2 groups,while the 2 groups were inconsistent with each other in the variation tendency(34.11±11.51,29.71±11.04,24.42±10.37,19.36±10.80 points,F=145.611,P=0.000; 32.65±11.94,30.77±11.90,29.66±12.46,28.64±13.38 points,F=8.764,P=0.000).There was no statistical difference in WOMAC ADL function scores between the 2 groups before the treatment and at 1 week after the beginning of the treatment(t=1.310,P=0.191; t=0.983,P=0.328),however,at 2 and 3 weeks after the beginning of the treatment,the WOMAC ADL function scores were lower in TN gel group compared to placebo group(t=4.554,P=0.000; t=7.542,P=0.000).⑤There was interaction between time factor and group factor in WOMAC total score(F=177.900,P=0.000).There was statistical difference in WOMAC total scores between the 2 groups in general,in other words,there was group effect(F=150.622,P=0.000).There was statistical difference in WOMAC total scores between different timepoints before and after the treatment,in other words,there was time effect(F=6.861,P=0.001).The WOMAC total scores presented a downward trend over time in the 2 groups,while the 2 groups were inconsistent with each other in the variation tendency(33.81±11.34,29.47±10.88,24.27±10.26,19.09±10.61 points,F=150.622,P=0.000; 32.46±11.72,30.60±11.66,29.55±12.23,28.55±13.16 points,F=8.694,P=0.000).There was no statistical difference in WOMAC total scores between the 2 groups before the treatment and at 1 week after the beginning of the treatment(t=1.224,P=0.223; t=1.063,P=0.289),however,at 2 and 3 weeks after the beginning of the treatment,the WOMAC total scores were lower in TN gel group compared to placebo group(t=4.662,P=0.000; t=7.820,P=0.000).⑥At 3 weeks after the beginning of the treatment,29 patients were controlled,66 good,248 fair and 88 poor in TN gel group; while 2 patients were controlled,6 good,14 fair and 122 poor in placebo group.The TN gel group surpassed placebo group in the total outcomes(Z=12.310,P=0.000).⑦All patients showed good compliance and finished the treatment as required except for 1 patient in TN gel group dropping out of the study.The mildly elevated transaminase(1 case)and mild local skin allergy(1 case)were found in TN gel group,while mild local skin allergy(4 cases)was found in placebo group.The transaminase returned to normal and the skin allergy subsided spontaneously after stopping the medication without any special treatment.There was no statistical difference in complication incidences between the 2 groups(χ2=3.593,P=0.058).Conclusion:External application of TN gel can relieve knee pain and stiffness and improve knee function in mild-to-moderate KOA patients with syndromes of kidney deficiency and tendon-vessel stasis,and it has high safety.

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(收稿日期:2020-05-19 本文编辑:时红磊)

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通讯作者:詹红生 E-mail:shgsyjs@139.com
更新日期/Last Update: 1900-01-01