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Official Journal of the Italian Association for Cutaneous Ulcers
Indexed/Abstracted in: EMBASE, Scopus, Emerging Sources Citation Index
Online ISSN 1827-1774
Nikol S. 1, Baumgartner I. 2, Van Belle E. 3, Diehm C. 4, Visoná A. 5, Capogrossi M. C. 6, Ferreira-Maldent N. 7, Gallino A. 8, Graham Wyatt M. 9, Dinesh Wijesinghe L. 10, Fusari M. 11, Stephan D. 12, Emmerich J. 13, Pompilio G. 14, Vermassen F. 15, Pham E. 16, Grek V. 16, Coleman M. 16, Meyer F. 16*
1 Department of Cardiology and Angiology, Universitätsklinikum, Münster, Germany
2 Department of Heart and Vascular Medicine (DHGE), Division of Angiology University of Bern, Bern, Switzerland
3 Department of Cardiology B and Hemodynamics, Hôpital Cardiologique, CHRU de Lille, France
4 Department of Internal Medicine and Vascular Medicine, Klinikum Karlsbad-Langensteinbach GmbH, Karlsbad, Germany
5 Department of Internal Medicine Angiology Unit, University of Padova Castelfranco Veneto, Italy
6 Vascular Pathology Laboratory Dermopathology “dell’Immacolata”, Rome, Italy
7 Department of Internal Medicine B Hôpital Bretonneau, Tours, France
8 Department of Cardiovascular Research Unit Ospedale San Giovanni, Bellinzona, Switzerland
9 Department of General Surgery Northern Vascular Center, Freeman Hospital Newcastle Upon Tyne, UK
10 Department of Vascular Surgery Royal Bournemouth Hospital, Bournemouth, UK
11 Deparment of Vascular Surgery Cliniche Gavazzeni, Bergamo, Italy
12 Department of Hypertension Vascular Diseases and Pharmacology, Hôpital Civil, Strasbourg, France
13 University Paris Descartes, INSERM, U765, Service de Médecine Vasculaire-HTA Paris, France
14 Department of Vascular Surgery Centro Cardiologico Monzino, Milano, Italy
15 Department of Vascular Surgery Ghent University Hospital, Gent, Belgium
16 Centelion SAS, Vitry sur Seine, France
Aim. 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).
Methods. In a doubleblind, 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).
Results. 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).
Conclusion. 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.