Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease - A phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication
Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease - A phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication
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DOI：
10.1161/01.cir.0000093398.16124.29
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发表时间：
2003-10-21
期刊：
影响因子：
37.8
通讯作者：
Annex, BH
中科院分区：
文献类型：
--
作者：
Rajagopalan, S;Mohler, ER;Annex, BH
背景-“治疗性血管生成”寻求通过新血管的生长来改善灌注。使用血管内皮生长因子的区域血管生成（RAVE）试验是腺病毒血管内皮生长因子（VEGF）基因转移治疗外周动脉疾病（PAD）的第一个主要随机研究。方法和结果-该2期、双盲、安慰剂对照研究设计用于测试肌肉内递送AdVEGF 121、一种编码血管内皮生长因子121-氨基酸亚型的复制缺陷型腺病毒，用于单侧PAD患者的下肢。总共有105例受试者在2次合格的平板运动试验中出现单侧运动限制性间歇性跛行，峰值步行时间（PWT）在1 - 10分钟之间，根据糖尿病状态分层，并随机分配至低剂量组（4 × 10（9）PU）AdVEGF 121、高剂量（4 × 10（10）PU）AdVEGF 121或安慰剂，在单次给药中对第一条腿进行20次肌内注射。主要疗效终点，12周时PWT的变化（DeltaPWT）在安慰剂组（1.8 ± 3.2分钟）、低剂量组（1.6 ± 1.9分钟）和高剂量组（1.5 ± 3.1分钟）之间没有差异。第12周和第26周时，组间的次要指标（包括DeltaPWT、踝臂指数、跛行发作时间和生活质量指标（SF-36和步行障碍问卷））也相似。AdVEGF 121给药与外周水肿增加有关。结论：在这项研究中，单次单侧肌肉注射AdVEGF 121与运动能力或生活质量的改善无关。本研究不支持局部给予单剂量VEGF（121）作为单侧PAD患者的治疗策略。
Background -"Therapeutic angiogenesis" seeks to improve perfusion by the growth of new blood vessels. The Regional Angiogenesis with Vascular Endothelial growth factor ( RAVE) trial is the first major randomized study of adenoviral vascular endothelial growth factor ( VEGF) gene transfer for the treatment of peripheral artery disease ( PAD).Methods and Results - This phase 2, double-blind, placebo-controlled study was designed to test the efficacy and safety of intramuscular delivery of AdVEGF121, a replication-deficient adenovirus encoding the 121-amino-acid isoform of vascular endothelial growth factor, to the lower extremities of subjects with unilateral PAD. In all, 105 subjects with unilateral exercise-limiting intermittent claudication during 2 qualifying treadmill tests, with peak walking time (PWT) between 1 to 10 minutes, were stratified on the basis of diabetic status and randomized to low-dose (4 x 10(9) PU) AdVEGF121, high-dose (4 x 10(10) PU) AdVEGF121, or placebo, administered as 20 intramuscular injections to the index leg in a single session. The primary efficacy end point, change in PWT (DeltaPWT) at 12 weeks, did not differ between the placebo (1.8 +/- 3.2 minutes), low-dose (1.6 +/- 1.9 minutes), and high-dose (1.5 +/- 3.1 minutes) groups. Secondary measures, including DeltaPWT, ankle-brachial index, claudication onset time, and quality-of-life measures (SF-36 and Walking Impairment Questionnaire), were also similar among groups at 12 and 26 weeks. AdVEGF121 administration was associated with increased peripheral edema.Conclusions - A single unilateral intramuscular administration of AdVEGF121 was not associated with improved exercise performance or quality of life in this study. This study does not support local delivery of single-dose VEGF(121) as a treatment strategy in patients with unilateral PAD.