Design of the DEFINE trial: Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib
Design of the DEFINE trial: Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib
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DOI：
10.1016/j.ahj.2009.07.028
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发表时间：
2009-10-01
影响因子：
4.8
通讯作者：
Barter, Philip
中科院分区：
文献类型：
--
作者：
Cannon, Christopher P.;Dansky, Hayes M.;Barter, Philip
背景：尽管他汀类药物可以降低低密度脂蛋白胆固醇(LDL-C)，但残余心血管(CV)风险仍然很高。目前正在研究提高高密度脂蛋白胆固醇(高密度脂蛋白胆固醇)的新疗法。ANACERAPIB是一种胆固醇酯转移蛋白(CETP)抑制剂，当单独或与他汀类药物一起使用时，它会升高高密度脂蛋白-C，降低低密度脂蛋白-C。另一类药物对血压、电解质和醛固酮水平的不良影响，到目前为止还没有在止痛药研究中被注意到。方法确定使用止痛药抑制CETP的有效性和耐受性(DEFINE)是一项随机、双盲、安慰剂对照试验，用于评估止痛药在冠心病(CHD)或CHID风险等效物患者中的有效性和安全性(临床试验。政府NCT00685776)。符合国家胆固醇教育计划-成人治疗小组III低密度脂蛋白-C治疗目标的患者，无论是否服用其他调脂药物，都要接受为期18个月的anacRapib、100 mg或安慰剂治疗，然后进行为期3个月的研究后随访。主要终点是低密度脂蛋白-C与基线的百分比变化以及anacetraib的安全性和耐受性。将在6个月和12个月的时间点进行全面的预先计划的临时安全分析，以检查关键安全终点的治疗效果，包括血压和电解质。考虑到本研究预期的事件数量有限，将使用预先计划的贝叶斯分析来解释心血管事件的分布。结果在20个国家和地区的153个中心对2757名患者进行了筛查，其中1,623名患者随机进入试验。这项试验的血脂结果、临床心血管事件和安全结果预计将于2010年公布。(《美国心脏杂志》2009；158：513-9。)
Background Residual cardiovascular (CV) risk often remains high despite statin therapy to lower low-density lipoprotein cholesterol (LDL-C). New therapies to raise high-density lipoprotein cholesterol (HDL-C) are currently being investigated. Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that raises HDL-C and reduces LDL-C when administered alone or with a statin. Adverse effects on blood pressure, electrolytes, and aldosterone levels, seen with another drug in this class, have not been noted in studies of anacetrapib to date.Methods Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib (DEFINE) is a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety profile of anacetrapib in patients with coronary heart disease (CHD) or CHID risk equivalents (clinical trials.gov NCT00685776). Eligible patients at National Cholesterol Education Program-Adult Treatment Panel III LDL-C treatment goal on a statin, with or without other lipid-modifying medications, are treated with anacetrapib, 100 mg, or placebo for 18 months, followed by a 3-month, poststudy follow-up. The primary end points are percent change from baseline in LDL-C and the safety and tolerability of anacetrapib. Comprehensive preplanned interim safety analyses will be performed at the 6- and 12-month time points to examine treatment effects on key safety end points, including blood pressure and electrolytes. A preplanned Bayesian analysis will be performed to interpret the CV event distribution, given the limited number of events expected in this study.Results A total of 2,757 patients were screened at 153 centers in 20 countries, and 1,623 patients were randomized into the trial. Lipid results, clinical CV events, and safety outcomes from this trial are anticipated in 2010. (Am Heart J 2009; 158:513-9.)