Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY 40213, USA.
Curr Med Res Opin. 2010 Apr;26(4):907-15. doi: 10.1185/03007991003645318.
Assess the long-term efficacy and safety of prescription omega-3-acid ethyl esters (P-OM3) coadministered with simvastatin in an extension of the Combination of Prescription Omega-3 Plus Simvastatin (COMBOS) trial.
COMBOS included hypertriglyceridemic patients (triglyceride [TG] >or=200 mg/dL and <500 mg/dL or >or=2.26 mmol/L and <5.64 mmol/L) with low density lipoprotein cholesterol (LDL-C) level no greater than 10% above the National Cholesterol Education Program, Adult Treatment Panel III treatment goal. After an 8-week lead-in phase with simvastatin 40 mg/day (which continued throughout the trial), subjects were randomized to 8 weeks of P-OM3 4 g/day or placebo. Completers were eligible to participate in a 24-month extension study. Those who received placebo + simvastatin in COMBOS switched to open-label P-OM3 + simvastatin ('Switchers'); those who received P-OM3 + simvastatin during COMBOS continued the same regimen (open-label) in the extension phase ('Non-switchers'). The primary endpoint was the difference between Non-switchers and Switchers in median percent change in non-high-density lipoprotein-cholesterol (non-HDL-C) from COMBOS end of treatment to Month 4 of the extension phase.
At Month 4 from COMBOS end of treatment, non-HDL-C was reduced by a median of 9.4% in Switchers and increased by 0.9% in Non-switchers (p < 0.001). For the total population (combined Non-switcher + Switcher population), the median percent change from COMBOS baseline to Months 4, 12, and 24 was -8.3%, -7.3%, and -8.9%, respectively (all p < 0.001). This extension study revealed no unexpected safety findings. A limitation of this study was a gap between completion of COMBOS and enrollment in the extension phase for some patients; however, a post-hoc non-HDL-C sensitivity analysis performed at the 4-month primary endpoint revealed no influence of gap on study results.
In this 24-month extension study, P-OM3 was generally well tolerated, and produced sustained reductions in non-HDL-C levels in simvastatin-treated patients with TG levels between 200 and 500 mg/dL (2.26 mmol/L and 5.64 mmol/L).
NCT00903409.
评估处方ω-3 酸乙酯（P-OM3）与辛伐他汀联合治疗在组合处方ω-3 加辛伐他汀（COMBOS）试验扩展中的长期疗效和安全性。
COMBOS 纳入了伴有高甘油三酯血症（甘油三酯 [TG] >或=200mg/dL 和 <500mg/dL 或 >或=2.26mmol/L 和 <5.64mmol/L）且低密度脂蛋白胆固醇（LDL-C）水平高于国家胆固醇教育计划成人治疗专家组 III 治疗目标 10%的患者。在辛伐他汀 40mg/天的 8 周导入期（整个试验期间持续）后，受试者被随机分配至 8 周的 P-OM3 4g/天或安慰剂。完成者有资格参加 24 个月的扩展研究。在 COMBOS 中接受安慰剂+辛伐他汀的患者转为开放标签 P-OM3+辛伐他汀（“Switchers”）；在 COMBOS 中接受 P-OM3+辛伐他汀的患者在扩展阶段继续接受相同的方案（开放标签）（“Non-switchers”）。主要终点是非 Switchers 和 Switchers 从 COMBOS 治疗结束到扩展阶段第 4 个月时非高密度脂蛋白胆固醇（non-HDL-C）的中位数百分比变化之间的差异。
在 COMBOS 治疗结束后的第 4 个月，Switchers 中非高密度脂蛋白胆固醇降低了中位数 9.4%，Non-switchers 中增加了 0.9%（p<0.001）。对于总人群（非 Switcher+Switcher 人群），从 COMBOS 基线到第 4、12 和 24 个月的中位数百分比变化分别为-8.3%、-7.3%和-8.9%（均<0.001）。这项扩展研究没有发现意外的安全性发现。本研究的一个局限性是一些患者在完成 COMBOS 和入组扩展阶段之间存在时间间隔；然而，在第 4 个月主要终点时进行的非高密度脂蛋白胆固醇敏感性分析显示，时间间隔对研究结果没有影响。
在这项 24 个月的扩展研究中，P-OM3 通常耐受良好，可使 TG 水平在 200-500mg/dL（2.26mmol/L 和 5.64mmol/L）的辛伐他汀治疗患者的非高密度脂蛋白胆固醇水平持续降低。
NCT00903409。
