海博麦布治疗原发性高胆固醇血症的有效性和安全性:多中心、随机、双盲、安慰剂平行对照Ⅲ期临床研究  

Efficacy and Safety of Hybutimibe in the Treatment of Primary Hypercholesterolemia:a Multicenter,Randomized,Double-blind,Placebo-controlled Phase Ⅲ Trial

作　　者：陈纪言 张宇辉[2] 肖文良[3] 魏琰[4] 郭小梅[5] 齐丽彤[6] 董吁钢[7] 赵水平[8] 周淑娴[9] 丁春华[10] 黄恺[11] 陈晞明[12] 陈晓平[13] 杨新春 霍勇[6] CHEN Jiyan;ZHANG Yuhui;XIAO Wenliang;WEI Yan;GUO Xiaomei;Qi Litong;DONG Yugang;ZHAO Shuiping;ZHOU Shuxian;DING Chunhua;HUANG Kai;CHEN Ximing;CHEN Xiaoping;YANG Xinchun;HUO Yong(Department of Cardiology,Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences,Guangzhou(510000),Guangdong,China)

机构地区：[1]广东省人民医院,广东省医学科学院心内科,广州市510000 [2]中国医学科学院,北京协和医学院,国家心血管病中心阜外医院心内科 [3]河北医科大学第三医院心内科 [4]哈励逊国际和平医院神经内科 [5]华中科技大学同济医学院附属同济医院心内科 [6]北京大学第一医院心内科 [7]中山大学附属第一医院心内科 [8]中南大学湘雅二医院心内科 [9]中山大学孙逸仙纪念医院心内科 [10]航天中心医院心内科 [11]华中科技大学附属协和医院心内科 [12]广州医科大学附属第三医院心内科 [13]四川大学华西医院心内科 [14]首都医科大学附属北京朝阳医院心脏中心

出　　处：《中国循环杂志》2022年第7期708-714,共7页Chinese Circulation Journal

基　　金：国家科技重大专项课题-重大新药创制(2013ZX09402101)。

摘　　要：目的:评估海博麦布治疗原发性高胆固醇血症的有效性和安全性。方法:本研究为多中心、随机、双盲、安慰剂平行对照的Ⅲ期临床试验。共纳入分析原发性高胆固醇血症患者373例,按2:1随机接受海博麦布(试验组,n=248)或安慰剂(对照组,n=125)20 mg/d治疗12周(治疗评价期)。延伸期持续40周,两组均口服海博麦布20 mg/d。主要疗效终点为第12周低密度脂蛋白胆固醇(LDL-C)较基线的变化率,次要疗效终点为治疗评价期和延伸期其他血脂指标的变化率,同时观察用药安全性。结果:第12周试验组LDL-C较基线的变化率为(-10.23±13.58)%,显著优于对照组(4.34±15.88)%,P<0.05。试验组非高密度脂蛋白胆固醇(non-HDL-C)、总胆固醇(TC)和载脂蛋白B(Apo B)的变化率分别为(-10.81±12.28)%、(-7.92±9.88)%和(-12.06±11.32)%,均显著优于对照组的(3.22±15.90)%、(2.18±11.68)%和(0.51±13.37)%(P均<0.05),而高密度脂蛋白胆固醇、甘油三酯和载脂蛋白AI变化率的差异无统计学意义。试验组与对照组不良反应的发生率在第12周分别为4.55%和8.40%,在延伸期分别为4.43%和7.07%,未发现新的或加重的与海博麦布可能相关的不良事件。结论:海博麦布可以有效降低原发性高胆固醇血症患者的LDL-C、non-HDL-C、TC和Apo B水平,降脂效果可长期持续,不良反应发生率低,耐受性好。Objectives: To evaluate the efficacy and safety of hybutimibe in treating primary hypercholesterolemia.Methods: This was a multi-center, randomized, double-blind, placebo-controlled phase Ⅲ clinical trial. A total of 373patients with primary hypercholesterolemia were randomized at 2:1 ratio to receive hybutimibe(20 mg/d, n=248) or placebo(20 mg/d, n=125) for 12 weeks. In the subsequent extension study, both groups received hybutimibe(20 mg/d) for 40 weeks.The primary endpoint was the percentage change of low-density lipoprotein cholesterol(LDL-C) from baseline at week 12.Secondary endpoints were the percentage changes of other blood lipid levels. Safety was also observed.Results: At week 12, the percentage change of LDL-C in the hybutimibe group was(-10.23 ± 13.58)%, significantly superior to(4.34 ± 15.88)% in the placebo group(P<0.05). The percentage changes of non-HDL-C([-10.81 ± 12.28]%vs. [3.22 ± 15.90]%), TC([-7.92 ± 9.88]% vs. [2.18 ± 11.68]%) and Apo B([-12.06 ± 11.32]% vs. [0.51 ± 13.37]%) in the hybutimibe group were significantly superior to those of the placebo group(all P<0.05), while there were no differences in the percentage changes of HDL-C, Apo AI and TG. The incidences of adverse reactions in the hybutimibe and placebo groups were 4.55% and 8.40% at week 12, and 4.43% and 7.07% at week 52, respectively. Neither new nor aggravated adverse events that might be associated with hybutimibe were observed during the extension study.Conclusions: Hybutimibe can reduce LDL-C, non-HDL-C, TC and Apo B levels in patients with primary hypercholesterolemia, with stable effects and low incidences of long-term adverse events.

关 键 词：原发性高胆固醇血症 海博麦布 随机对照试验 低密度脂蛋白胆固醇 

分 类 号：R541.4[医药卫生—心血管疾病]