Mohler Emile R, Rajagopalan Sanjay, Olin Jeffrey W, Trachtenberg Jeffrey D, Rasmussen Henrik, Pak Raphael, Crystal Ronald G
Department of Internal Medicine, Section of Vascular Medicine, Division of Cardiology, University of Pennsylvania Health System, Philadelphia, PA, USA.
Vasc Med. 2003;8(1):9-13. doi: 10.1191/1358863x03vm460oa.
Critical limb ischemia (CLI) is typified by rest pain and/or tissue necrosis secondary to advanced peripheral arterial disease (PAD) and is characterized by diminution in limb perfusion at rest. We tested the safety of an angiogenic strategy with CI-1023 (Ad(GV)VEGF121.10), a replication-deficient adenovirus encoding human vascular endothelial growth factor isoform 121 in patients with CLI as part of a phase I trial. Fifteen subjects >35 years of age with CLI and angiographic disease involving the infra-inguinal vessels underwent intramuscular injection of CI-1023 (4 x 10(8) to 4 x 10(10) particle units, n = 13) or placebo (n = 2). All of the patients tolerated the injection well and there were no serious complications related to the procedure. Transient edema was noted in one patient. A total of 79 adverse events were reported over the course of one year. One death (day 136) and one malignancy (day 332) occurred in the CI-1023 group. CI-1023 appears to be well tolerated and safe for single-dose administration in patients with critical limb ischemia due to PAD. Further studies are needed to determine the efficacy of this form of therapeutic angiogenesis.
严重肢体缺血（CLI）的典型表现为继发于晚期外周动脉疾病（PAD）的静息痛和/或组织坏死，其特征是静息时肢体灌注减少。作为一项I期试验的一部分，我们在CLI患者中测试了CI-1023（Ad(GV)VEGF121.10）这种血管生成策略的安全性，CI-1023是一种编码人血管内皮生长因子121亚型的复制缺陷型腺病毒。15名年龄大于35岁、患有CLI且血管造影显示疾病累及腹股沟下血管的受试者接受了CI-1023（4×10⁸至4×10¹⁰颗粒单位，n = 13）或安慰剂（n = 2）的肌肉注射。所有患者对注射耐受良好，且未出现与该操作相关的严重并发症。有一名患者出现了短暂性水肿。在一年的时间里共报告了79起不良事件。CI-1023组发生了1例死亡（第136天）和1例恶性肿瘤（第332天）。对于因PAD导致严重肢体缺血的患者，CI-1023单剂量给药似乎耐受性良好且安全。需要进一步研究来确定这种治疗性血管生成形式的疗效。
