title: Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia.
abstract: 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.
authors.affiliation: Department of Cardiology and Angiology, Universitätsklinikum, Münster, Germany. nikol@uni-muenster.de
authors.forename: Sigrid
authors.initials: S
authors.lastname: Nikol
authors.forename: Iris
authors.initials: I
authors.lastname: Baumgartner
authors.forename: Eric
authors.initials: E
authors.lastname: Van Belle
authors.forename: Curt
authors.initials: C
authors.lastname: Diehm
authors.forename: Adriana
authors.initials: A
authors.lastname: Visoná
authors.forename: Maurizio C
authors.initials: MC
authors.lastname: Capogrossi
authors.forename: Nicole
authors.initials: N
authors.lastname: Ferreira-Maldent
authors.forename: Augusto
authors.initials: A
authors.lastname: Gallino
authors.forename: Michael Graham
authors.initials: MG
authors.lastname: Wyatt
authors.forename: Lasantha Dinesh
authors.initials: LD
authors.lastname: Wijesinghe
authors.forename: Melissa
authors.initials: M
authors.lastname: Fusari
authors.forename: Dominique
authors.initials: D
authors.lastname: Stephan
authors.forename: Joseph
authors.initials: J
authors.lastname: Emmerich
authors.forename: Giulio
authors.initials: G
authors.lastname: Pompilio
authors.forename: Frank
authors.initials: F
authors.lastname: Vermassen
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Pham
authors.forename: Vincent
authors.initials: V
authors.lastname: Grek
authors.forename: Michael
authors.initials: M
authors.lastname: Coleman
authors.forename: François
authors.initials: F
authors.lastname: Meyer
mesh_terms: 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
chemical_list: D010919:Placebos; D016220:Fibroblast Growth Factor 1