黄葵胶囊治疗2型糖尿病肾脏病患者白蛋白尿疗效及安全性的临床研究

Evaluation of the efficacy and safety of Abelmoschus manihot alone and in combination with irbesartan for reduction of albuminuria in patients with type 2 diabetes and diabetic kidney disease

目的探讨黄葵胶囊治疗2型糖尿病肾脏病患者白蛋白尿的疗效及安全性。方法为多中心、随机、双盲和平行对照试验。选取2017年5月至2021年3月在江苏省9家三甲医院(南京中医药大学附属医院、常州市第一人民医院、徐州市第一人民医院、无锡市人民医院、南通大学附属医院、泰州市中医院、苏州大学附属第一医院、东南大学附属中大医院、常州市中医医院)就诊的2型糖尿病肾脏病患者作为研究对象,采用分层区组随机的方法将患者分配到厄贝沙坦组[厄贝沙坦(150 mg/次,1次/d)+黄葵胶囊模拟剂(2.5 g/次,3次/d)]、黄葵胶囊组[黄葵胶囊(2.5 g/次,3次/d)+厄贝沙坦模拟剂(150 mg/次,1次/d)]和联合治疗组[厄贝沙坦(150 mg/次,1次/d)+黄葵胶囊(2.5 g/次,3次/d)]治疗,试验周期为24周。检测患者基线及治疗24周后尿肌酐及尿白蛋白,并计算尿白蛋白/肌酐比值(UACR),观察UACR较基线的变化值和变化率,记录患者不良事件、不良反应、严重不良事件、严重不良反应、导致退出的不良事件的发生情况并计算发生率。采用单因素方差分析、χ^(2)检验或Fisher精确概率法进行组间比较。结果共纳入413例2型糖尿病肾脏病患者。其中,厄贝沙坦组138例,黄葵胶囊组137例,联合治疗组138例。治疗24周后,3组患者UACR变化值分别为(-89.07±51.17)、(-146.06±45.52)和(-262.31±39.08)mg/g,黄葵胶囊组与厄贝沙坦组UACR变化值差异没有统计学意义(P=0.087),联合治疗组与厄贝沙坦组间差异有统计学意义(P<0.001)。治疗24周后,3组UACR变化率分别为(-5.21±6.12)%、(-11.89±5.75)%和(-28.56±4.65)%,黄葵胶囊组与厄贝沙坦组UACR变化率差异没有统计学意义(P=0.395),联合治疗组与厄贝沙坦组差异有统计学意义(P<0.001)。治疗24周后,3组患者的不良事件、不良反应、严重不良事件、严重不良反应发生率差异均无统计学意义(P>0.05)。结论联合使用厄贝沙坦和黄葵胶囊可以进一步降低2型糖尿病肾脏病患者UACR水平,在控制2型糖尿病肾脏病患者白蛋白尿的治疗中具有较好的疗效和安全性。

Objective To evaluate the efficacy and safety of Abelmoschus manihot(A.Manihot)alone and in combination with irbesartan,for reduction of albuminuria in patients with type 2 diabetic kidney disease.Methods A multicenter randomized double-blind and parallel controlled clinical trial was performed in 9 hospitals of Jiangsu Province(Affiliated Hospital of Nanjing University of Chinese Medicine,First People′s Hospital of Changzhou,First People′s Hospital of Xuzhou,Wuxi People′s Hospital,Affiliated Hospital of Nantong University,Taizhou Hospital of Traditional Chinese Medicine,First Affiliated Hospital of Soochow University,Zhongda Hospital,Southeast University,Changzhou Hospital of Traditional Chinese Medicine)from May 2017 to March 2021.Huangkui capsule,as a traditional Chinese medicine,is made from the ethanol extract of flowers in A.Manihot.All enrolled patients were randomly assigned to the irbesartan group[irbesartan tablets(150 mg/dose,1 dose/day)+Huangkui capsule simulant(2.5 g/dose,3 doses/day)],Huangkui capsule group[Huangkui capsule(2.5 g/dose,3 doses/day)+irbesartan simulant(150 mg/dose,1 dose/day)],and combined treatment group[irbesartan tablets(150 mg/dose,1 dose/day)+Huangkui capsule(2.5 g/dose,3 doses/day)].The duration of intervention was 24 weeks.Urinary creatinine and urinary albumin were detected at baseline and 24 weeks after treatment,and the urinary albumin-to-creatinine ratio was calculated to observe the change value and rate of UACR compared with baseline.The occurrence of adverse events,adverse reactions,serious adverse events,serious adverse events,and adverse events leading to withdrawal were recorded and the incidence was calculated.One-way analysis of variance(ANOVA),χ^(2) test or Fisher's exact test were used to compare among groups.Results A total of 413 patients with type 2 diabetic kidney disease were included,including 138 in the irbesartan group,137 in the Huangkui capsule group and 138 in the combined treatment group.After 24 weeks of treatment,the UACR changes of three groups were(-89.07±51.17)mg/g in the irbesartan group,(-146.06±45.52)mg/g in the Huangkui capsule group,and(-262.31±39.08)mg/g in the combined treatment group.The rate of UACR change was(-5.21±6.12)%in the irbesartan group,(-11.89±5.75)%in the Huangkui capsule group,and(-28.56±4.65)%in the combined treatment group,respectively.There were significant differences between the combined treatment group and the irbesartan group in the change value and rate of UACR(P<0.001),while there were no statistical differences between the Huangkui capsule group and irbesartan group(P>0.05).After 24 weeks of treatment,there were no significant differences in the incidence of adverse events,adverse reactions,serious adverse events and serious adverse reactions among the 3 groups(P>0.05).Conclusion The combination of irbesartan and Huangkui capsule can reduce the level of UACR in patients with type 2 diabetic kidney disease,and it shows good efficacy and safety in the treatment of albuminuria in patients with type 2 diabetic kidney disease.