甘海胃康胶囊治疗功能性消化不良的前瞻性、随机、双盲、安慰剂对照临床研究

Ganhai Weikang capsule in the treatment of functional dyspepsia:a prospective randomized,double-blind,placebo-controlled parallel clinical study

目的:探讨甘海胃康胶囊治疗功能性消化不良(FD)的有效性和安全性。方法:采用随机、双盲、安慰剂平行对照、多中心、优效性临床研究设计,于2018年3月至2020年4月,从海军军医大学第一附属医院(上海长海医院)、黑龙江省中医院、天津市中医药研究院附属医院、山东大学齐鲁医院、浙江大学附属第一医院、首都医科大学附属北京中医医院、中南大学湘雅三医院7个三级甲等医院中,选择以消化不良症状就诊的门诊患者324例,经内镜和病理检查诊断为慢性非萎缩性胃炎,符合FD罗马Ⅳ诊断标准。受试者按照1∶1比例随机分为甘海胃康组和安慰剂组,甘海胃康组给予甘海胃康胶囊,安慰剂组给予甘海胃康胶囊模拟剂,两组患者用药方法均为餐前口服,2.4 g/次、3次/d,疗程均为4周。主要疗效指标为4周后的临床总有效率,次要疗效指标为上腹痛、上腹部烧灼感、餐后饱胀不适、早饱感的症状评分变化情况,安全性评价指标包括实验室检查和不良事件等。采用卡方检验和Wilcoxon秩和检验进行统计学分析。结果:共320例FD患者纳入全分析集,其中甘海胃康组161例,安慰剂组159例,共298例患者纳入符合方案集(PPS),甘海胃康组和安慰剂组各149例。全分析集和PPS分析均显示,甘海胃康组临床总有效率高于安慰剂组[分别为84.5%(136/161)比44.0%(70/159)和83.9%(125/149)比46.3%(69/149)],差异均有统计学意义( χ^(2)=57.07、46.32,均 P<0.001)。全分析集和PPS分析均显示,甘海胃康组主要症状总评分治疗前后差值和各单项症状(上腹痛、上腹部烧灼感、餐后饱胀不适、早饱感)评分治疗前后差值均高于安慰剂组[全分析集:10分(7分,14分)比5分(3分,11分)、3分(2分,4分)比2分(0分,3分)、2分(0分,4分)比1分(0分,3分)、3分(1分,4分)比2分(1分,3分)、2分(0分,4分)比1分(0分,3分)。PPS:10分(7分,13分)比5分(3分,11分)、3分(2分,4分)比2分(0分,3分)、2分(0分,4分)比1分(0分,2分)、3分(1分,4分)比2分(1分,3分)、2分(0分,4分)比1分(0分,3分)],差异均有统计学意义(全分析集: Z=5.80、5.91、3.19、3.72、3.30;PPS: Z=5.14、5.11、2.86、3.21、2.84;均 P<0.01)。全分析集和PPS分析均显示,甘海胃康组主要症状总改善率和各单项症状(上腹痛、上腹部烧灼感、餐后饱胀不适、早饱感)改善率均高于安慰剂组[全分析集:77.8%(54.6%,91.3%)比42.9%(28.6%,61.5%)、100.0% (60.0%,100.0%)比50.0% (25.0%,60.0%)、100.0% (50.0%,100.0%)比50.0% (25.0%,100.0%)、71.4% (33.3%,100.0%)比41.4%(25.0%,66.7%)、100.0% (50.0%,100.0%)比50.0% (20.0%,100.0%)。PPS:77.8% (54.2%,89.5%)比44.0% (28.6%,65.0%)、100.0% (60.0%,100.0%)比50.0% (25.0%,100.0%)、100.0% (50.0%,100.0%)比50.0% (25.0%,100.0%)、71.4% (33.3%,100.0%)比46.4% (25.0%,66.7%)、100.0% (50.0%,100.0%)比50.0% (20.0%,100.0%)],差异均有统计学意义(全分析集: Z=8.60、7.72、4.98、4.24、5.61;PPS: Z=7.90、7.03、4.49、3.88、4.83;均 P<0.001)。治疗2周后,甘海胃康组主要症状总评分,以及单项症状上腹痛、上腹部烧灼感、早饱感症状评分与治疗前评分差值均高于安慰剂组[5.0分(3.0分,8.0分)比4.0分(2.0分,6.0分)、2.0分(1.0分,2.0分)比2.0分(0.0分,2.0分)、1.5分(0.0分,2.0分)分比1.0分(0.0分,2.0分)、1.5分(0.0分,2.0分)比1.0分(0.0分,2.0分)],差异均有统计学意义( Z=2.95、3.44、2.43、2.79,均 P<0.05)。甘海胃康组与安慰剂组不良事件发生率比较[0.6%(1/163)比0(0/159)]差异无统计学意义( P>0.05)。 结论:甘海胃康胶囊治疗FD的临床总有效率高于安慰剂,且具有较好的安全性。

Objective To explore the efficacy and safety of Ganhai Weikang capsule(GWC)in the treatment of functional dyspepsia(FD).Methods A randomized,double-blind,placebo-controlled parallel,multi-center,superiority clinical trial was conducted.From March 2018 to April 2020,totally 324 patients with dyspepsia symptoms,who were diagnosed as chronic non-atrophic gastritis by endoscopy and pathology and met the RomeⅣdiagnostic criteria for FD from 7 top hospitals were enrolled,including the First Affiliated Hospital of Naval Medical University(Shanghai Changhai Hospital),Heilongjiang Hospital of Traditional Chinese Medicine,Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital,Qilu Hospital of Shandong University,the First Affiliated Hospital of Zhejiang University,Beijing Hospital of Traditional Chinese Medicine of Capital Medical University and the Third Xiangya Hospital of Central South University.The patients were randomly divided into the GWC group and the placebo group according to the ratio of 1∶1.The patients of GWC group were given GWC and the patients of placebo group were given GWC capsule simulant.The patients of both groups orally took capsules before meals,2.4 g each time and 3 times per day,and the course of treatment was 4 weeks.The main efficacy index was the total clinical effective rate after 4 weeks,and the secondary efficacy index was the changes of clinical symptom scores of upper abdominal pain,upper abdominal burning,postprandial fullness and early satiety.The safety index included laboratory tests and adverse events.Chi-square test and Wilcoxon rank sum test were used for statistical analysis.Results A total of 320 FD patients were enrolled in the full analysis set(FAS),which included 161 cases in GWC group and 159 cases in placebo group.A total of 298 cases were in the per-protocol set(PPS),149 cases each in GWC group and placebo group.The results of FAS and PPS both showed that the total clinical effective rates of the GWC group were higher than those of the placebo group(84.5%,136/161 vs.44.0%,70/159 and 83.9%,125/149 vs.46.3%,69/149),and the differences were statistically significant(χ^(2)=57.07 and 46.32,both P<0.001).In addition,the differences of the total score of main symptoms and each symptom(upper abdominal pain,upper abdominal burning,postprandial fullness and early satiety)before and after treatment of GWC group were all higher than those of the placebo group(FAS:10(7,14)vs.5(3,11);3(2,4)vs.2(0,3);2(0,4)vs.1(0,3);3(1,4)vs.2(1,3);2(0,4)vs.1(0,3).PPS:10(7,13)vs.5(3,11);3(2,4)vs.2(0,3);2(0,4)vs.1(0,2);3(1,4)vs.2(1,3);2(0,4)vs.1(0,3)),and the differences were statistically significant(FAS:Z=5.80,5.91,3.19,3.72 and 3.30;PPS:Z=5.14,5.11,2.86,3.21 and 2.84;all P<0.01).The results of FAS and PPS indicated that the improvement rates of main symptoms and each symptom(upper abdominal pain,upper abdominal burning,postprandial fullness and early satiety)of GWC group were all higher than those of the placebo group(FAS:77.8%(54.6%,91.3%)vs.42.9%(28.6%,61.5%);100.0%(60.0%,100.0%)vs.50.0%(25.0%,60.0%);100.0%(50.0%,100.0%)vs.50.0%(25.0%,100.0%);71.4%(33.3%,100.0%)vs.41.4%(25.0%,66.7%);100.0%(50.0%,100.0%)vs.50.0%(20.0%,100.0%).PPS:77.8%(54.2%,89.5%)vs.44.0%(28.6%,65.0%);100.0%(60.0%,100.0%)vs.50.0%(25.0%,100.0%);100.0%(50.0%,100.0%)vs.50.0%(25.0%,100.0%);71.4%(33.3%,100.0%)vs.46.4%(25.0%,66.7%);100.0%(50.0%,100.0%)vs.50.0%(20.0%,100.0%)),and the differences were statistically significant(FAS:Z=8.60,7.72,4.98,4.24 and 5.61;PPS:Z=7.90,7.03,4.49,3.88 and 4.83;all P<0.001).After 2 weeks of treatment,the differences of the total score of main symptoms and score of each symptom(upper abdominal pain,upper abdominal burning and early satiety)before and after treatment of GWC group were all higher than those of the placebo group(5.0(3.0,8.0)vs.4.0(2.0,6.0);2.0(1.0,2.0)vs.2.0(0.0,2.0);1.5(0.0,2.0)vs.1.0(0.0,2.0);1.5(0.0,2.0)vs.1.0(0.0,2.0)),and the differences were statistically significant(Z=2.95,3.44,2.43 and 2.79,all P<0.05).There was no significant difference in the incidence of adverse events between the GWC group and the placebo group(0.6%,1/163 vs.0,0/159).Conclusion The clinical total effective rate of GWC in the treatment of FD is superior to that of placebo and it has good safety.