Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, USA.
Cardiovasc Drugs Ther. 2012 Apr;26(2):181-7. doi: 10.1007/s10557-012-6373-5.
Considerable interest has focused on the development of therapies that target the functionality of high-density lipoproteins (HDL). Upregulation of endogenous synthesis of the major protein on HDL particles, apolipoprotein A-I (apoA-I), represents a novel approach to generation of new HDL particles. The Study of Quantitative Serial Trends in Lipids with Apolipoprotein A-I Stimulation (SUSTAIN, NCT01423188) study aims to evaluate the lipid efficacy, safety and tolerability of an apoA-I inducer (RVX-208). The ApoA-I Synthesis Stimulation and Intravascular Ultrasound for Coronary Atheroma Regression Evaluation (ASSURE, NCT01067820) study aims to evaluate the effect of RVX-208 on plaque burden.
In SUSTAIN, 172 patients with low levels of HDL-C will be randomized to receive RVX-208 100 mg bid or placebo for 24 weeks. The primary efficacy parameter will be the percentage change in HDL-C levels. In ASSURE, 310 patients with angiographic coronary artery disease and low HDL-C levels will be randomized to receive RVX-208 100 mg bid or placebo for 26 weeks. The primary efficacy parameter will be the nominal change in percent atheroma volume (PAV), determined by analysis of intravascular ultrasound (IVUS) images of matched coronary artery segments acquired at baseline and at 26-week follow-up. The effect of RVX-208 on other lipid and inflammatory markers, safety and tolerability will also be assessed in both studies.
ApoA-I induction represents a potential novel strategy to reduce cardiovascular risk, by generating nascent HDL particles. These studies will provide early evaluation of the effects of RVX-208 on lipids and atherosclerotic plaque.
人们对靶向高密度脂蛋白（HDL）功能的治疗方法产生了浓厚的兴趣。上调 HDL 颗粒上主要蛋白载脂蛋白 A-I（apoA-I）的内源性合成，代表了产生新的 HDL 颗粒的一种新方法。定量系列趋势研究中的载脂蛋白 A-I 刺激（SUSTAIN，NCT01423188）旨在评估 apoA-I 诱导剂（RVX-208）的脂质疗效、安全性和耐受性。载脂蛋白 A-I 合成刺激和血管内超声用于冠状动脉粥样斑块消退评估（ASSURE，NCT01067820）研究旨在评估 RVX-208 对斑块负担的影响。
在 SUSTAIN 中，172 名 HDL-C 水平较低的患者将被随机分为 RVX-208 100mg bid 或安慰剂组，治疗 24 周。主要疗效参数为 HDL-C 水平的百分比变化。在 ASSURE 中，310 名有血管造影冠状动脉疾病和低 HDL-C 水平的患者将被随机分为 RVX-208 100mg bid 或安慰剂组，治疗 26 周。主要疗效参数将是通过分析基线和 26 周随访时获得的匹配冠状动脉节段的血管内超声（IVUS）图像确定的粥样斑块体积百分比变化（PAV）。这两项研究还将评估 RVX-208 对其他脂质和炎症标志物的影响、安全性和耐受性。
apoA-I 诱导代表了通过产生新生的 HDL 颗粒来降低心血管风险的潜在新策略。这些研究将早期评估 RVX-208 对脂质和动脉粥样硬化斑块的影响。
