Randomized, double-blinded and controlled trial of Xiaopi Zhitong Decoction in the treatment of functional dyspepsia with syndrome of spleen deficiency and Qi stagnation
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摘要: 目的 评价消痞止痛方治疗功能性消化不良(脾虚气滞证)的临床疗效和安全性。方法 采用多中心、随机、双盲、阳性药物和安慰剂平行对照的方法，把117例功能性消化不良患者随机分为试验组、对照组和安慰剂组，分别予消痞止痛方、香砂六君子汤和安慰剂治疗4周。主要疗效指标为总体症状应答率，次要疗效指标为总体症状积分改善率和单项症状有效率。疗效分析分为全分析集(FAS)以及符合方案集(PPS)分析。结果 试验组、对照组和安慰剂组总体症状应答率的PPS集分析分别为76.9%、42.4%和27.8%(P< 0.01)，FAS集分析分别为75.6%、36.8%和26.3%(P< 0.01)；3组总体症状改善率的PPS集分析分别为41.1%、30.1%和24.1%(P< 0.05)，FAS集分析分别为41.1%、25.5%和22.9%(P< 0.05)；试验组各单项症状有效率在FAS和PPS分析集中均显著优于安慰剂组，试验组的早饱感和上腹烧灼感的有效率在FAS分析集中显著优于对照组(P< 0.05)。3组患者不良反应发生率比较差异无统计学意义(P>0.05)。结论 消痞止痛方能安全有效治疗脾虚气滞证功能性消化不良，其疗效优于香砂六君子汤。Abstract: Objective To evaluate the clinical effect and safety of Xiaopi Zhitong Decoction in the treatment of functional dyspepsia with syndrome of spleen deficiency and Qi stagnation.Methods A total of 117 patients with functional dyspepsia were divided into three groups, the test group, control group and placebo group, and were given Xiaopi Zhitong Decoction, Xiangsha Liujunzi Decoction and the placebo respectively. This was a 4-week multicenter, randomized, double-blinded, positive and placebo parallel controlled, clinical trial. The primary efficacy indicators were the overall symptom response rate, and the secondary efficacy indicators were overall symtoms score improvement rate and individual symptom effective rate.Results The overall clinical symptoms response rates of the test group, control group and placebo group were 76.9%, 42.4% and 27.8% (P< 0.01) by PPS analysis, 75.6%, 36.8% and 26.3% (P< 0.01) respectively by FAS analysis. The total symptom improvement rates of the three groups were 41.1%, 30.1% and 24.1% (P< 0.05) respectively by PPS, 41.1%, 25.5% and 22.9% (P< 0.05) respectively by FAS. The individual symptom effective rate in the test group was significantly better than that in the placebo group in both FAS and PPS analysis sets, and the efficiency of early satiety and epigastric burning in the test group was significantly higher than that in the control group in FAS analysis sets (P< 0.05). There was no statistical difference in the incidence of adverse reactions among the three groups (P> 0.05).Conclusion Xiaopi Zhitong Decoction can safely and effectively improve the clinical symptoms of functional dyspepsia, and even more effective than Xiangsha Liujunzi Decoction.
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表 1 3组基线资料比较
X±S 组别 例数 年龄/岁 性别/例 BMI 总体症状积分/分 男 女 试验组 41 47.44±17.41 16 25 22.33±3.44 10.10±2.44 对照组 38 55.74±13.61 17 21 22.33±3.27 10.03±2.30 安慰剂组 38 50.39±13.53 13 25 22.61±3.14 9.61±2.38 P 0.051 0.643 0.911 0.638 
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表 2 3组总体症状应答率比较
例 分析集 应答例数 无应答例数 总应答率/% P PPS < 0.001 试验组 30 9 76.91)2) 对照组 14 19 42.4 安慰剂组 10 26 27.8 FAS < 0.001 试验组 31 10 75.61)2) 对照组 14 24 36.8 安慰剂组 10 28 26.3 与对照组比较，1)P < 0.01；与安慰剂组比较，2)P < 0.01。
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表 3 3组总体症状积分和改善率比较
X±S 分析集 例数 总体症状积分/分 总体症状积分改善率/% 治疗前 治疗4周 PPS 试验组 39 10.13±2.43 5.83±1.531)2)3) 41.12)3) 对照组 33 10.03±2.43 6.73±1.311) 30.1 安慰剂组 36 9.69±2.41 7.28±2.281) 24.1 FAS 试验组 41 10.10±2.44 5.85±1.541)2)3) 41.12)3) 对照组 38 10.03±2.30 7.24±1.881) 25.5 安慰剂组 38 9.61±2.38 7.32±2.221) 22.9 与同组治疗前比较，1)P < 0.05；与对照组比较，2)P < 0.05；与安慰剂组比较，3)P < 0.05。
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表 4 3组单项症状有效率比较(PPS)
例 症状 试验组 对照组 安慰剂组 P 有效 无效 有效率/% 有效 无效 有效率/% 有效 无效 有效率/% 餐后饱胀 35 4 89.71) 27 3 90.0 24 11 68.6 0.025 早饱感 25 4 86.21) 20 8 71.4 15 12 55.6 0.040 上腹痛 26 4 86.71) 13 7 65.0 16 11 59.3 0.056 上腹烧灼感 25 4 86.21) 14 9 60.9 9 8 52.9 0.033 与安慰剂组比较，1)P < 0.05。
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表 5 3组单项症状有效率比较(FAS)
例 症状 试验组 对照组 安慰剂组 P 有效 无效 有效率/% 有效 无效 有效率/% 有效 无效 有效率/% 餐后饱胀 35 4 89.71) 28 8 77.8 24 13 64.9 0.034 早饱感 25 4 86.21)3) 20 12 62.5 15 12 55.6 0.033 上腹痛 26 5 83.91) 14 8 63.6 16 13 55.2 0.050 上腹烧灼感 25 4 86.22)4) 14 13 51.9 9 9 50.0 0.008 与安慰剂组比较，1)P < 0.05，2)P < 0.01；与对照组比较，3)P < 0.05，4)P < 0.01。
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[1] Ford AC, Mahadeva S, Carbone MF, et al. Functional dyspepsia[J]. Lancet, 2020, 396(10263): 1689-1702. doi: 10.1016/S0140-6736(20)30469-4
[2] 吴柏瑶, 张法灿, 梁列新. 功能性消化不良的流行病学[J]. 胃肠病学和肝病学杂志, 2013, 22(1): 85-90. https://www.cnki.com.cn/Article/CJFDTOTAL-WCBX201301031.htm
[3] Stanghellini V, Chan FK, Hasler WL, et al. Gastroduodenal Disorders[J]. Gastroenterology, 2016, 150(6): 1380-1392. doi: 10.1053/j.gastro.2016.02.011
[4] 中华中医药学会脾胃病分会, 张声生. 功能性消化不良中医诊疗专家共识意见(2017)[J]. 中华中医药杂志, 2017, 32(6): 2595-2598. https://www.cnki.com.cn/Article/CJFDTOTAL-BXYY201706072.htm
[5] Suzuki H, Matsuzaki J, Fukushima Y, et al. Randomized clinical trial: rikkunshito in the treatment of functional dyspepsia--a multicenter, double-blind, randomized, placebo-controlled study[J]. Neurogastroenterol Motil, 2014, 26(7): 950-961. doi: 10.1111/nmo.12348
[6] 吕林, 唐旭东, 王凤云, 等. 从"脾主运化"理论探讨论治功能性胃肠病[J]. 时珍国医国药, 2016, 27(1): 160-162. https://www.cnki.com.cn/Article/CJFDTOTAL-SZGY201601063.htm
[7] 中国中西医结合学会消化系统疾病专业委员会. 功能性消化不良中西医结合诊疗共识意见(2017年)[J]. 中国中西医结合消化杂志, 2017, 25(12): 889-894. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXPW201712001.htm
[8] Lv L, Wang FY, Ma XX, et al. Efficacy and safety of Xiangsha Liujunzi granules for functional dyspepsia: A multi-center randomized double-blind placebo-controlled clinical study[J]. World J Gastroenterol, 2017, 23(30): 5589-5601. doi: 10.3748/wjg.v23.i30.5589
[9] 任小军, 陈英. 功能性消化不良中医证型研究进展[J]. 江西中医药, 2020, 51(4): 78-80. https://www.cnki.com.cn/Article/CJFDTOTAL-JXZY202004027.htm
[10] Kim DY, Delgado-Aros S, Camilleri M, et al. Noninvasive measurement of gastric accommodation in patients with idiopathic nonulcer dyspepsia[J]. Am J Gastroenterol, 2001, 96(11): 3099-3105. doi: 10.1111/j.1572-0241.2001.05264.x
[11] Takahashi T. Pathophysiological significance of neuronal nitric oxide synthase in the gastrointestinal tract[J]. J Gastroenterol, 2003, 38(5): 421-430. doi: 10.1007/s00535-003-1094-y
[12] 王惠临, 张立平. 基于网络药理学探讨四逆散治疗功能性消化不良的作用机制[J]. 世界中医药, 2021, 16(10): 1507-1513. https://www.cnki.com.cn/Article/CJFDTOTAL-SJZA202110002.htm
[13] Oshima T, Okugawa T, Tomita T, et al. Generation of dyspeptic symptoms by direct acid and water infusion into the stomachs of functional dyspepsia patients and healthy subjects[J]. Aliment Pharmacol Ther, 2012, 35(1): 175-182. doi: 10.1111/j.1365-2036.2011.04918.x
[14] 贾子尧, 林瑞超, 马志强, 等. 四逆散药理作用和临床应用文献研究[J]. 辽宁中医药大学学报, 2017, 19(6): 159-162. https://www.cnki.com.cn/Article/CJFDTOTAL-LZXB201706054.htm
[15] 高双静, 翁棉伟, 章明, 等. 乌贝散加味联合西药治疗HP相关性消化性溃疡的Meta分析[J]. 中医药临床杂志, 2020, 32(10): 1859-1867. https://www.cnki.com.cn/Article/CJFDTOTAL-AHLC202010019.htm
[16] Enck P, Klosterhalfen S. Placebo Responses and Placebo Effects in Functional Gastrointestinal Disorders[J]. Front Psychiatry, 2020, 11: 797.
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