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

作　　者：赵静 Tostivint Isabelle 许陵冬 黄继汉[4] Gambotti Laetitia Boffa Jean-Jacques 杨敏[7] 王玲[8] 孙铸兴[9] 陈晓岚[10] Liou-Schischmanoff Amélie Baumelou Alain 马腾[12] 卢国元[13] 李玲[14] 陈岱[15] Piéroni Laurence 刘炳凯 秦笑 何伟明 王跃娟 顾丰 孙伟[1] Zhao Jing;Tostivint Isabelle;Xu Lingdong;Huang Jihan;Gambotti Laetitia;Boffa Jean-Jacques;Yang Min;Wang Ling;Sun Zhuxing;Chen Xiaolan;Liou-Schischmanoff Amélie;Baumelou Alain;Ma Teng;Lu Guoyuan;Li Ling;Chen Dai;Piéroni Laurence;Liu Bingkai;Qin Xiao;He Weiming;Wang Yuejuan;Gu Harvest F.;Sun Wei(Department of Nephrology,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China;Department of Nephrology,Sorbonne University,Pitié-Salpêtrière Hospital,Paris 75013,France;Centre of Integrative Chinese Medicine,Sorbonne University,Pitié-Salpêtrière Hospital,Paris 75013,France;Center for Drug Clinical Research,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Clinical Research,National Cancer Institute,Boulogne-Billancourt 92100,France;Department of Nephrology,Sorbonne University,Hospital Tenon,Paris 75020,France;Department of Nephrology,First People′s Hospital of Changzhou,Changzhou 213004,China;Department of Nephrology,First People′s Hospital of Xuzhou,Xuzhou 221002,China;Department of Nephrology,Wuxi People′s Hospital,Wuxi 214023,China;Department of Nephrology,Affiliated Hospital of Nantong University,Nantong 226006,China;Department of Pharmacy,Sorbonne University,Pitié-Salpêtrière,Paris 75013,France;Department of Nephrology,Taizhou Hospital of Traditional Chinese Medicine,Taizhou 225399,China;Department of Nephrology,First Affiliated Hospital of Soochow University,Suzhou 215006,China;Department of Endocrinology,Zhongda Hospital,Southeast University,Nanjing 210009,China;Department of Nephrology,Changzhou Hospital of Traditional Chinese Medicine,Changzhou 213004,China;Department of Biochemistry-Hormonology,Sorbonne University,Hospital Tenon,Paris 75020,France;School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Nanjing 211199,China)

机构地区：[1]南京中医药大学附属医院肾内科,南京210029 [2]法国巴黎索邦大学附属比提耶-萨勒伯特医院肾内科,巴黎75013 [3]法国巴黎索邦大学附属比提耶-萨勒伯特医院中西医结合部,巴黎75013 [4]上海中医药大学药物临床研究中心,上海201203 [5]法国布洛涅-比扬古国家肿瘤研究所临床研究部,布洛涅-比扬古92100 [6]法国巴黎索邦大学附属德隆医院肾内科,巴黎75020 [7]常州市第一人民医院肾内科,常州213004 [8]徐州市第一人民医院肾内科,徐州221002 [9]无锡市人民医院肾内科,无锡214023 [10]南通大学附属医院肾内科,南通226006 [11]法国巴黎索邦大学附属比提耶-萨勒伯特医院药学部,巴黎75013 [12]泰州市中医院肾内科,泰州225399 [13]苏州大学附属第一医院肾内科,苏州215006 [14]东南大学附属中大医院内分泌科,南京210009 [15]常州市中医医院肾内科,常州213004 [16]法国巴黎索邦大学附属德隆医院荷尔蒙学生物化学部,巴黎75020 [17]中国药科大学基础医学与临床药学学院,南京211199

出　　处：《中华糖尿病杂志》2023年第6期517-525,共9页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：法国巴黎公立医院集团课题(COMPL126,P131001);国家中医药管理局中医药科技研究专项(GZY-KJS-2019-017);国家中医药管理局中医药国际合作专项(GJZX2016005);南京市科学技术委员会国际联合研发项目(201402068)。

摘　　要：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�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 grou

关 键 词：糖尿病 2型 糖尿病肾脏病 白蛋白尿 黄葵胶囊 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学] R696.2[医药卫生—临床医学]