Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia
Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia
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DOI：
10.1007/s00380-015-0677-x
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发表时间：
2016-05-01
影响因子：
1.5
通讯作者：
Sakata, Ryuzo
中科院分区：
文献类型：
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作者：
Kumagai, Motoyuki;Marui, Akira;Sakata, Ryuzo
作为治疗性血管生成的一种形式，我们试图研究使用生物可降解明胶水凝胶的碱性成纤维细胞生长因子（bFGF）缓释系统在严重肢体缺血（CLI）患者中的安全性和有效性。我们进行了一项I-IIa期研究，分析了10名CLI患者在缺血肢体肌内注射200 μ g bFGF明胶水凝胶微球后的情况。主要终点是治疗后4周和24周的安全性和经皮氧分压（TcO 2）。随访期间，无死亡或严重手术相关不良事件。24周后，TcO 2（28.4 +/- A 8.4 vs. 46.2 +/- A 13.0 mmHg，治疗前vs 24周后，p < 0.01）显示出显著改善。关于次要终点，6分钟内行走的距离（255 +/- A 105 vs. 318 +/- A 127 m，p = 0.02），Rutherford分级（4.4 +/- A 0.5 vs. 3.1 +/- A 1.4，p = 0.02），静息痛量表（1.7 +/- A 1.0对比1.2 +/- A 1.3，p = 0.03），并且紫绀量表（2.0 +/- A 1.1对比0.9 +/- A 0.9，p < 0.01）也显示改善。所有患者血中bFGF水平均在正常范围内。对动脉硬化闭塞症（n = 7）或血栓闭塞性脉管炎（Buerger病）（n = 3）患者的亚组分析显示，两个亚组的TcO 2均显著改善。TcO 2在患有或不患有慢性肾脏疾病的患者之间没有差异。生物可降解明胶水凝胶缓释bFGF可能为CLI患者提供一种安全有效的血管生成形式。
As a form of therapeutic angiogenesis, we sought to investigate the safety and efficacy of a sustained-release system of basic fibroblast growth factor (bFGF) using biodegradable gelatin hydrogel in patients with critical limb ischemia (CLI). We conducted a phase I-IIa study that analyzed 10 CLI patients following a 200-mu g intramuscular injection of bFGF-incorporated gelatin hydrogel microspheres into the ischemic limb. Primary endpoints were safety and transcutaneous oxygen pressure (TcO2) at 4 and 24 weeks after treatment. During the follow-up, there was no death or serious procedure-related adverse event. After 24 weeks, TcO2 (28.4 +/- A 8.4 vs. 46.2 +/- A 13.0 mmHg for pretreatment vs after 24 weeks, p < 0.01) showed significant improvement. Regarding secondary endpoints, the distance walked in 6 min (255 +/- A 105 vs. 318 +/- A 127 m, p = 0.02), the Rutherford classification (4.4 +/- A 0.5 vs. 3.1 +/- A 1.4, p = 0.02), the rest pain scale (1.7 +/- A 1.0 vs. 1.2 +/- A 1.3, p = 0.03), and the cyanotic scale (2.0 +/- A 1.1 vs. 0.9 +/- A 0.9, p < 0.01) also showed improvement. The blood levels of bFGF were within the normal range in all patients. A subanalysis of patients with arteriosclerosis obliterans (n = 7) or thromboangiitis obliterans (Buerger's disease) (n = 3) revealed that TcO2 had significantly improved in both subgroups. TcO2 did not differ between patients with or without chronic kidney disease. The sustained release of bFGF from biodegradable gelatin hydrogel may offer a safe and effective form of angiogenesis for patients with CLI.