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01-05-2016 | Original Article

Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia

Authors: Motoyuki Kumagai, Akira Marui, Yasuhiko Tabata, Takahide Takeda, Masaya Yamamoto, Atsushi Yonezawa, Shiro Tanaka, Shigeki Yanagi, Toshiko Ito-Ihara, Takafumi Ikeda, Toshinori Murayama, Satoshi Teramukai, Toshiya Katsura, Kazuo Matsubara, Koji Kawakami, Masayuki Yokode, Akira Shimizu, Ryuzo Sakata

Published in: Heart and Vessels | Issue 5/2016

Abstract

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-μg 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 ± 8.4 vs. 46.2 ± 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 ± 105 vs. 318 ± 127 m, p = 0.02), the Rutherford classification (4.4 ± 0.5 vs. 3.1 ± 1.4, p = 0.02), the rest pain scale (1.7 ± 1.0 vs. 1.2 ± 1.3, p = 0.03), and the cyanotic scale (2.0 ± 1.1 vs. 0.9 ± 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.

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Title: Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia
Authors: Motoyuki Kumagai
Akira Marui
Yasuhiko Tabata
Takahide Takeda
Masaya Yamamoto
Atsushi Yonezawa
Shiro Tanaka
Shigeki Yanagi
Toshiko Ito-Ihara
Takafumi Ikeda
Toshinori Murayama
Satoshi Teramukai
Toshiya Katsura
Kazuo Matsubara
Koji Kawakami
Masayuki Yokode
Akira Shimizu
Ryuzo Sakata
Publication date: 01-05-2016
Publisher: Springer Japan
Published in: Heart and Vessels / Issue 5/2016
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI: https://doi.org/10.1007/s00380-015-0677-x

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