Results from a phase II multicenter, double-blind placebo-controlled study of Del-1 (VLTS-589) for intermittent claudication in subjects with peripheral arterial disease
Results from a phase II multicenter, double-blind placebo-controlled study of Del-1 (VLTS-589) for intermittent claudication in subjects with peripheral arterial disease
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DOI：
10.1016/j.ahj.2007.01.038
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发表时间：
2007-05-01
影响因子：
4.8
通讯作者：
Rocha-Singh, Krishna
中科院分区：
文献类型：
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作者：
Grossman, Paul Michael;Mendelsohn, Farrell;Rocha-Singh, Krishna
本研究比较了VLTS-589（编码血管基质蛋白Del-1与poloxam188联合的质粒）与poloxam188对照治疗中重度外周动脉疾病患者的间歇性跛行。方法入选双侧间歇性跛行且峰值步行时间（PWT）在1 - 10分钟之间的2个合格跑步机试验（重复性，彼此在25%以内）的受试者。患者接受VLTS-589或poloxam188对照，每条下肢肌肉注射21次（每条下肢42 mL）。除了安全性和耐受性外，与基线相比的疗效评估包括以下内容：90天PWT（主要终点）的变化，跛行发病时间的变化，踝肱指数（ABI）的变化以及生活质量测量的变化。结果105例患者随机接受治疗。在30、90和180天的随访期间，与基线值相比，两个治疗组的平均PWT、跛行起始时间和ABI均显著增加，主要终点和次要终点组间无显著差异。此外，两组在随访时均表现出与基线相比生活质量的显著改善，组间无显著差异。两组的严重不良事件相似，均与治疗无关。结论肌内注射Del-1表达质粒和对照组在30、90和180天的运动能力均显著改善。与Del-1质粒相关的结果测量没有差异。
Background This study compared VLTS-589 (plasmid encoding the angiomatrix protein Del-1 in conjunction with poloxamer 188) with poloxamer 188 control, for the treatment of intermittent claudication in patients with moderate to severe peripheral arterial disease.Methods Subjects with bilateral intermittent claudication and peak walking time (PWT) between I and 10 minutes on 2 qualifying (reproducible; within 25% of each other) treadmill tests were enrolled. Patients received VLTS-589 or poloxamer 188 control, administered as 2 1 intramuscular injections to each lower extremity (42 mL in each extremity). In addition to safety and tolerability, efficacy evaluations compared to baseline included the following: change in PWT at 90 days (primary end point), change in claudication onset time, change in ankle brachial index (ABI), and change in quality of life measures.Results A total of 105 patients were randomized and treated. During the 30, 90, and 180 days follow-up, mean PWT, claudication onset time, and ABI were significantly increased compared to baseline values in both treatment groups with no significant difference between groups in the primary or secondary end points. In addition, both groups demonstrated significantly improved quality of life at follow-up vs baseline, with no significant differences between groups. Serious adverse events were similar in both groups-none were definitely treatment-related.Conclusion Intramuscular delivery of both Del-1 expressing plasmid and the control resulted in significant improvement in exercise capacity compared to baseline at 30, 90, and 180 days. There was no difference in outcome measures associated with the Del-1 plasmid.