TY - JOUR
T1 - Results of a double-blind, placebo-controlled study to assess the safety of intramuscular injection of hepatocyte growth factor plasmid to improve limb perfusion in patients with critical limb ischemia
AU - Powell, Richard J.
AU - Simons, Michael
AU - Mendelsohn, Farrel O.
AU - Daniel, George
AU - Henry, Timothy D.
AU - Koga, Minako
AU - Morishita, Ryuichi
AU - Annex, Brian H.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2008/7/1
Y1 - 2008/7/1
N2 - Background - The Study to Assess the Safety of Intramuscular Injection of Hepatocyte Growth Factor Plasmid to Improve Limb Perfusion in Patients With Critical Limb Ischemia (HGF-STAT trial) determined the effect of hepatocyte growth factor (HGF) plasmid on safety and limb tissue perfusion as measured by transcutaneous oxygen tension (TcPo2) in patients with critical limb ischemia (CLI). Methods and results - Randomized patients with rest pain or ischemic ulcers and TcPo2 <40 mm Hg and/or toe pressure <50 mm Hg received placebo or HGF-plasmid intramuscular injection as follows: 0.4 mg at days 0, 14, and 28 (low dose); 4.0 mg at days 0 and 28 (middle dose); or 4.0 mg at days 0, 14, and 28 (high dose). Patients were evaluated for safety, changes in TcPo2 and ankle and toe pressure, amputation, and wound healing. Ninety-three of 104 treated patients were evaluated for safety (mean age 70 years, 63% male, 53% diabetic, 64% with tissue loss, mean ankle-brachial index 0.41, and mean toe pressure 26 mm Hg). Adverse events occurred in 86% of the patients, most of which were related to CLI or comorbid conditions and were not different between groups. TcPo2 (mean±SE) increased at 6 months in the high-dose group (24.0±4.2 mm Hg, 95% CI 15.5 to 32.4 mm Hg) compared with the placebo (9.4±4.2 mm Hg, 95% CI 0.9 to 17.8), low-dose (11.1±3.7 mm Hg, CI 3.7 to 18.7 mm Hg), and middle-dose (7.3±4.8 mm Hg, CI -2.2 to 17.0 mm Hg) groups (ANCOVA P=0.0015). There was no difference between groups in secondary end points, including ankle-brachial index, toe-brachial index, pain relief, wound healing, or major amputation. Conlusions - Intramuscular injection of HGF plasmid was safe and well tolerated. Larger studies to determine whether HGF plasmid can improve wound healing and limb salvage in patients with CLI are warranted.
AB - Background - The Study to Assess the Safety of Intramuscular Injection of Hepatocyte Growth Factor Plasmid to Improve Limb Perfusion in Patients With Critical Limb Ischemia (HGF-STAT trial) determined the effect of hepatocyte growth factor (HGF) plasmid on safety and limb tissue perfusion as measured by transcutaneous oxygen tension (TcPo2) in patients with critical limb ischemia (CLI). Methods and results - Randomized patients with rest pain or ischemic ulcers and TcPo2 <40 mm Hg and/or toe pressure <50 mm Hg received placebo or HGF-plasmid intramuscular injection as follows: 0.4 mg at days 0, 14, and 28 (low dose); 4.0 mg at days 0 and 28 (middle dose); or 4.0 mg at days 0, 14, and 28 (high dose). Patients were evaluated for safety, changes in TcPo2 and ankle and toe pressure, amputation, and wound healing. Ninety-three of 104 treated patients were evaluated for safety (mean age 70 years, 63% male, 53% diabetic, 64% with tissue loss, mean ankle-brachial index 0.41, and mean toe pressure 26 mm Hg). Adverse events occurred in 86% of the patients, most of which were related to CLI or comorbid conditions and were not different between groups. TcPo2 (mean±SE) increased at 6 months in the high-dose group (24.0±4.2 mm Hg, 95% CI 15.5 to 32.4 mm Hg) compared with the placebo (9.4±4.2 mm Hg, 95% CI 0.9 to 17.8), low-dose (11.1±3.7 mm Hg, CI 3.7 to 18.7 mm Hg), and middle-dose (7.3±4.8 mm Hg, CI -2.2 to 17.0 mm Hg) groups (ANCOVA P=0.0015). There was no difference between groups in secondary end points, including ankle-brachial index, toe-brachial index, pain relief, wound healing, or major amputation. Conlusions - Intramuscular injection of HGF plasmid was safe and well tolerated. Larger studies to determine whether HGF plasmid can improve wound healing and limb salvage in patients with CLI are warranted.
KW - Angiogenesis
KW - Atherosclerosis
KW - Critical limb ischemia
KW - Gene therapy
KW - Peripheral vascular disease
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UR - http://www.scopus.com/inward/citedby.url?scp=50949129278&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.107.727347
DO - 10.1161/CIRCULATIONAHA.107.727347
M3 - Article
C2 - 18559703
AN - SCOPUS:50949129278
SN - 0009-7322
VL - 118
SP - 58
EP - 65
JO - Circulation
JF - Circulation
IS - 1
ER -