非诺贝特酸降脂疗效和安全性评价--一项中国区随机、双盲、安慰剂对照临床研究

Efficacy and Safety of Fenofibric Acid in Chinese Hyperlipidemia Patients:a Randomized,Doubleblinded and Placebo-controlled Clinical Trial

目的:验证非诺贝特酸在中国人群中的降脂疗效和安全性。方法:采用多中心双盲随机对照试验设计,将不同类型的高脂血症患者分为重度、中度高甘油三酯血症(HTG)及混合型血脂异常(MD)3个队列,1:1随机化将不同队列患者分为非诺贝特酸组与安慰剂组,分别给予非诺贝特酸(135mg,每天1次)或安慰剂治疗12周,主要终点为甘油三酯(TG)从基线至治疗12周时的变化百分比,次要终点为其他血脂成分和高敏C反应蛋白的变化百分比,同时记录不良事件的发生情况。结果:重度(n=52)、中度(n=23)HTG和MD(n=52)三个队列患者中,非诺贝特酸组的TG水平从基线至治疗12周分别降低(49.12±29.19)%、(47.95±25.19)%和(49.79±19.28)%,安慰剂组分别降低(18.88±40.69)%、(8.11±29.86)%和升高了(10.42±73.04)%,非诺贝特酸组TG降低幅度与安慰剂组相比差异均有统计学意义(重度HTG队列P<0.017,中度HTG和MD队列P均<0.05)。非诺贝特酸组高密度脂蛋白胆固醇(HDL-C)升高(25.51±21.45)%、(24.55±24.73)%和(23.60±27.38)%,安慰剂组升高(1.91±20.42)%、(2.40±9.32)%和(7.13±19.12)%,差异均有统计学意义(P均<0.05)。非诺贝特酸组发生率>5%的不良事件包括上呼吸道感染(10.9%)、腹痛(6.3%)及血肌酐水平升高(6.3%),与安慰剂组比较发生率差异无统计学意义。结论:对于中国重度、中度HTG患者或已接受他汀类药物治疗的MD患者,非诺贝特酸可显著降低TG水平,并升高HDL-C水平,不良事件发生率与服用安慰剂相似。

Objectives:Fenofibric acid is extracted from the widely used hypolipemic fenofibrate,nowadays being approved for marketing around numerous nations and regions,nonetheless not in China.Present trial evaluated the efficacy and safety in the Chinese hypertriglyceridemia population.Methods:This is a multi-center,randomized,double-blind,placebo-controlled phaseⅢclinical trial.Patients from 3 different cohorts,including severe hypertriglyceridemia(HTG),moderate HTG and mixed-dyslipidemia(MD),were randomized at 1:1 ratio to receive fenofibric acid 135 mg or placebo daily for 12 weeks.The primary endpoint was the percentage change of triglyceridemia(TG)from baseline at week 12.Secondary endpoints were the percentage changes of other blood lipid indexes.At the same time,the incidence of medical adverse events was observed.Results:Among the three cohorts of patients with severe HTG(n=52),moderate HTG(n=23)and MD(n=52),the TG levels in the fenofibric acid-treated group decreased by(49.12±29.19)%,(49.95±25.19)%and(49.79±19.28)%,respectively from baseline to 12 weeks,while the corresponding placebo groups decreased by(18.88±40.69)%,(8.11±29.86)%and increased by(10.42±73.04)%,respectively from baseline to 12 weeks.The differences between treatment and placebo groups were statistically significant(P<0.017 for severe HTG cohort,P<0.05 for moderate and MD cohort).The high-density lipoprotein cholesterol(HDL-C)in the fenofibric acid-treated group increased by(25.51±21.45)%,(24.55±24.73)%,and(23.60±27.38)%,and the placebo group increased by(1.91±20.42)%,(2.40±9.32)%and(7.13±19.12)%,respectively,the differences between the two groups were statistically significant(allP<0.05).In the fenofibric acid group,adverse events with incidence>5%included upper respiratory tract infection(10.9%),abdominal pain(6.3%),and increased serum creatinine levels(6.3%),rates of adverse events were similar between the two groups(P>0.05).Conclusions:Fenofibric acid can significantly reduce triglycerides and elevate HDL-C levels safely in Chinese patients with severe to moderate HTG without statin or MD patients on top of statin therapy.