Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia: A double-blind randomized trial

被引:246
作者
Kusumanto, Y. H.
Van Weel, V.
Mulder, N. H.
Smit, A. J.
Van den Dungen, J. J. A. M.
Hooymans, J. M. M.
Sluiter, W. J.
Tio, R. A.
Quax, P. H. A.
Gans, R. O. B.
Dullaart, R. P. F.
Hospers, G. A. P.
机构
[1] Univ Groningen, Med Ctr, Dept Med Oncol, NL-9700 RB Groningen, Netherlands
[2] Univ Groningen, Dept Internal Med, NL-9700 RB Groningen, Netherlands
[3] Leiden Univ, Med Ctr, Dept Vasc Surg, NL-2333 ZA Leiden, Netherlands
[4] Univ Groningen, Dept Vasc Surg, NL-9700 RB Groningen, Netherlands
[5] Univ Groningen, Dept Ophthalmol, NL-9700 RB Groningen, Netherlands
[6] Univ Groningen, Dept Pathol & Lab Med, NL-9700 RB Groningen, Netherlands
[7] Univ Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands
[8] TNO, Gaubius Lab, PG, NL-2301 CE Leiden, Netherlands
[9] Univ Groningen, Dept Endocrinol, NL-9700 RB Groningen, Netherlands
关键词
D O I
10.1089/hum.2006.17.683
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 0836 [生物工程]; 090102 [作物遗传育种]; 100705 [微生物与生化药学];
摘要
Despite advances in revascularization techniques, limb salvage and relief of pain cannot be achieved in many diabetic patients with diffuse peripheral vascular disease. Our objective was to determine the effect of intramuscular administration of phVEGF(165) (vascular endothelial growth factor gene-carrying plasmid) on critical limb ischemia (CLI) compared with placebo (0.9% NaCl). A double-blind, placebo-controlled study was performed in 54 adult diabetic patients with CLI. The primary end point was the amputation rate at 100 days. Secondary end points were a 15% increase in pressure indices (ankle-to-brachial index and toe-to-brachial index), clinical improvement (skin, pain, and Quality of Life score), and safety. In patients (n = 27) treated with placebo versus phVEGF(165)-treated patients (n=27) the following results were found: 6 amputations versus 3 (p = not significant [NS]); hemodynamic improvement in 1 versus 7 (p = 0.05); improvement in skin ulcers, 0 versus 7 (p = 0.01); decrease in pain, 2 versus 5 (p = NS); and overall, 3 versus 14 responding patients (p = 0.003). No grade 3 or 4 adverse effects were seen in these patients. We conclude that this small, randomized gene therapy study failed to meet the primary objective of significant amputation reduction. However, significant and meaningful improvement was found in patients treated with a VEGF(165)-containing plasmid. There were no substantial adverse events.
引用
收藏
页码:683 / 691
页数:9
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