Rajagopalan Sanjay, Mohler Emile R, Lederman Robert J, Mendelsohn Farrell O, Saucedo Jorge F, Goldman Corey K, Blebea John, Macko Jennifer, Kessler Paul D, Rasmussen Henrik S, Annex Brian H
Department of Internal Medicine, Section of Vascular Medicine, Division of Cardiovascular Medicine, University of Michigan Health System, Ann Arbor, USA.
Circulation. 2003 Oct 21;108(16):1933-8. doi: 10.1161/01.CIR.0000093398.16124.29. Epub 2003 Sep 22.
"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).
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 (4x10(9) PU) AdVEGF121, high-dose (4x10(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.
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 VEGF121 as a treatment strategy in patients with unilateral PAD.
“治疗性血管生成”旨在通过新血管的生长来改善灌注。血管内皮生长因子区域血管生成（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）的首个大型随机研究。
这项2期双盲安慰剂对照研究旨在测试向单侧PAD患者下肢肌肉注射AdVEGF121（一种编码血管内皮生长因子121个氨基酸异构体的复制缺陷型腺病毒）的疗效和安全性。共有105名在2次合格的跑步机测试中出现单侧运动受限间歇性跛行、峰值步行时间（PWT）在1至10分钟之间的受试者，根据糖尿病状态进行分层，并随机分为低剂量（4×10⁹PU）AdVEGF121组、高剂量（4×10¹⁰PU）AdVEGF121组或安慰剂组，在一次疗程中向患侧腿进行20次肌肉注射。主要疗效终点为12周时PWT的变化（ΔPWT），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）之间无差异。次要指标，包括ΔPWT、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）在12周和26周时各组之间也相似。注射AdVEGF121与外周水肿增加有关。
在本研究中，单次单侧肌肉注射AdVEGF121与运动表现或生活质量改善无关。本研究不支持将单剂量VEGF121局部给药作为单侧PAD患者的治疗策略。
