A Randomized Controlled, Phase 2 Trial of the Viral Serpin Serp-1 in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention
A Randomized Controlled, Phase 2 Trial of the Viral Serpin Serp-1 in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention
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DOI：
10.1161/circinterventions.110.953885
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发表时间：
2010-12-01
影响因子：
5.6
通讯作者：
Lucas, Alexandra
中科院分区：
文献类型：
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作者：
Tardif, Jean-Claude;L'Allier, Philippe L.;Lucas, Alexandra
血管炎症可导致斑块不稳定和急性冠状动脉综合征（ACS）。病毒产生有效的免疫调节蛋白，调节关键的炎症途径。粘液瘤病毒衍生的丝氨酸蛋白酶抑制剂Serp-1减少血管损伤模型中的炎性细胞侵袭和斑块生长我们的目的是评估Serp-1的安全性和有效性ACS患者接受经皮冠状动脉intervention.Methods和Results-This双盲试点试验包括48 ACS患者接受经皮冠状动脉介入治疗随机分配到Serp-1的剂量为5 μ g/kg（n=19）或15 μ g/kg（n=17）或安慰剂（n=12）。Serp-1在干预前即刻、24和48小时后静脉推注。评估患者的安全性（主要目标）和疗效结局，包括生物标志物分析。在6个月时通过血管内超声评价支架内新生内膜增生。Serp-1组和安慰剂组之间的关键安全性结局（包括凝血参数和不良事件）无差异。Serp-1在8、16、24和54小时观察到肌钙蛋白I水平呈剂量依赖性降低（P
Background-Vascular inflammation can lead to plaque instability and acute coronary syndromes (ACS). Viruses produce potent immunomodulating proteins that regulate key inflammatory pathways. A myxoma virus-derived serpin Serp-1 reduces inflammatory cell invasion and plaque growth in vascular injury models. Our objective was to evaluate the safety and efficacy of Serp-1 in patients with ACS undergoing percutaneous coronary intervention.Methods and Results-This double-blind pilot trial included 48 ACS patients undergoing percutaneous coronary intervention randomly assigned to Serp-1 at doses of 5 mu g/kg (n=19) or 15 mu g/kg (n=17) or to placebo (n=12). Serp-1 was given by intravenous bolus immediately before intervention and 24 and 48 hours later. Patients were assessed for safety (primary objective) and efficacy outcomes, including biomarker analysis. In-stent neointimal hyperplasia was evaluated by intravascular ultrasound at 6 months. Key safety outcomes including coagulation parameters and adverse events did not differ between Serp-1 and placebo groups. A dose-dependent reduction in troponin I levels was observed with Serp-1 at 8, 16, 24, and 54 hours (P