Journal Article

Therapeutic Angiogenesis With Intramuscular NV1FGF Improves Amputation-free Survival in Patients With Critical Limb Ischemia

Fusari, Melissa, Pompilio, Giulio, Baumgartner, Iris, Graham Wyatt, Michael, Stephan, Dominique, Pham, Emmanuel, Meyer, François, Dinesh Wijesinghe, Lasantha, Emmerich, Joseph, Capogrossi, Maurizio C, Diehm, Curt, Nikol, Sigrid, Grek, Vincent, Gallino, Augusto, Vermassen, Frank, Coleman, Michael, Van Belle, Eric, Visoná, Adriana, Ferreira-Maldent, Nicole

2008

Overview

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.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Aged / Amputation / Angiogenesis / Cardiology / Cardiovascular Diseases - genetics / Coronary Circulation - genetics / Coronary Circulation - physiology / Disease / Dose-Response Relationship, Drug / Double-Blind Method / Female / Fibroblast Growth Factor 1 - genetics / Fibroblast Growth Factor 1 - metabolism / Gene therapy / Genetic Techniques / Genetic Therapy - methods / Growth factors / Hospitals / Humans / Injections, Intramuscular / Internal medicine / Ischemia / Male / Medical prognosis / Medicine / Middle Aged / Mortality / Myocardial Revascularization - methods / Neovascularization, Physiologic - genetics / Neovascularization, Physiologic - physiology / Placebos / Plasmids / Proportional Hazards Models / Quality of life / Risk / Ulcers / Vascular surgery