Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia.
This study evaluated the efficacy and safety of intramuscular administration of NV1FGF, a plasmid-based angiogenic gene delivery system for local expression of fibroblast growth factor 1 (FGF-1), versus placebo, in patients with critical limb ischemia (CLI). In a double-blind, randomized, placebo-controlled, European, multinational study, 125 patients in whom revascularization was not considered to be a suitable option, presenting with nonhealing ulcer(s), were randomized to receive eight intramuscular injections of placebo or 2.5 ml of NV1FGF at 0.2 mg/ml on days 1, 15, 30, and 45 (total 16 mg: 4 x 4 mg). The primary end point was occurrence of complete healing of at least one ulcer in the treated limb at week 25. Secondary end points included ankle brachial index (ABI), amputation, and death. There were 107 patients eligible for evaluation. Improvements in ulcer healing were similar for use of NV1FGF (19.6%) and placebo (14.3%; P = 0.514). However, the use of NV1FGF significantly reduced (by twofold) the risk of all amputations [hazard ratio (HR) 0.498; P = 0.015] and major amputations (HR 0.371; P = 0.015). Furthermore, there was a trend for reduced risk of death with the use of NV1FGF (HR 0.460; P = 0.105). The adverse event incidence was high, and similar between the groups. In patients with CLI, plasmid-based NV1FGF gene transfer was well tolerated, and resulted in a significantly reduced risk of major amputation when compared with placebo.
Nikol
Sigrid
S
Department of Cardiology and Angiology, Universitätsklinikum, Münster, Germany. nikol@uni-muenster.de
Baumgartner
Iris
I
Van Belle
Eric
E
Diehm
Curt
C
Visoná
Adriana
A
Capogrossi
Maurizio C
MC
Ferreira-Maldent
Nicole
N
Gallino
Augusto
A
Wyatt
Michael Graham
MG
Wijesinghe
Lasantha Dinesh
LD
Fusari
Melissa
M
Stephan
Dominique
D
Emmerich
Joseph
J
Pompilio
Giulio
G
Vermassen
Frank
F
Pham
Emmanuel
E
Grek
Vincent
V
Coleman
Michael
M
Meyer
François
F
D000368:Aged; D002318:Cardiovascular Diseases / Q000235:genetics; D003326:Coronary Circulation / Q000235:genetics* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000235:genetics* / Q000378:metabolism; D005821:Genetic Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D009204:Myocardial Revascularization / Q000379:methods*; D018919:Neovascularization, Physiologic / Q000235:genetics* / Q000502:physiology; D010919:Placebos; D016016:Proportional Hazards Models; D012306:Risk
D010919:Placebos; D016220:Fibroblast Growth Factor 1