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 × 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.
Department of Cardiology and Angiology, Universitätsklinikum, Münster, Germany.
Sigrid
S
Nikol
Department of Heart and Vascular Medicine (DHGE), Division of Angiology, University of Bern, Bern, Switzerland.
Iris
I
Baumgartner
Department of Cardiology B and Hemodynamics, Hôpital Cardiologique, CHRU de Lille, France.
Eric
E
Van Belle
Department of Internal Medicine and Vascular Medicine, Klinikum Karlsbad-Langensteinbach GmbH, Karlsbad, Germany.
Curt
C
Diehm
Department of Internal Medicine, Angiology Unit, University of Padova, Castelfranco Veneto, Italy.
Adriana
A
Visoná
Laboratorio di patologia Vascolare, Istituto Dermopatico dell'Immacolata, Roma, Italy.
Maurizio C
MC
Capogrossi
Department of Internal Medicine B, Hôpital Bretonneau, Tours, France. Electronic address: nikol@uni-muenster.de.
Nicole
N
Ferreira-Maldent
Department of Cardiovascular Research Unit, Ospedale San Giovanni, Bellinzona, Switzerland.
Augusto
A
Gallino
Department of General Surgery, Northern Vascular Center, Freeman Hospital, Newcastle Upon Tyne, UK.
Michael
M
Graham Wyatt
Department of Vascular Surgery, Royal Bournemouth Hospital, Bournemouth, UK.
Lasantha
L
Dinesh Wijesinghe
Deparment of Vascular Surgery, Cliniche Gavazzeni, Bergamo, Italy.
Melissa
M
Fusari
Department of Hypertension, Vascular Diseases and Pharmacology, Hôpital Civil, Strasbourg, France.
Dominique
D
Stephan
University Paris Descartes, INSERM U765, Service de Médecine Vasculaire-HTA, Paris, France.
Joseph
J
Emmerich
Department of Vascular Surgery, Centro Cardiologico Monzino, Milano, Italy.
Giulio
G
Pompilio
Department of Vascular Surgery, Ghent University Hospital, Gent, Belgium.
Frank
F
Vermassen
Centelion SAS, Vitry sur Seine, France.
Emmanuel
E
Pham
Centelion SAS, Vitry sur Seine, France.
Vincent
V
Grek
Centelion SAS, Vitry sur Seine, France.
Michael
M
Coleman
Centelion SAS, Vitry sur Seine, France.
François
F
Meyer