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: Sigrid Nikol, Iris Baumgartner, Eric Van Belle, Curt Diehm, Adriana Visoná, Maurizio C Capogrossi, Nicole Ferreira-Maldent, Augusto Gallino, Michael Graham Wyatt, Lasantha Dinesh Wijesinghe, Melissa Fusari, Dominique Stephan, Joseph Emmerich, Giulio Pompilio, Frank Vermassen, Emmanuel Pham, Vincent Grek, Michael Coleman, François Meyer, TALISMAN 201 investigators
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 16 Issue 5 Pg. 972-8 (May 2008) ISSN: 1525-0024 [Electronic] United States
• PMID: 18388929 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Placebos
• Fibroblast Growth Factor 1

Topics

• Aged
• Cardiovascular Diseases (genetics)
• Coronary Circulation (genetics, physiology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Fibroblast Growth Factor 1 (genetics, metabolism)
• Genetic Techniques
• Genetic Therapy (methods)
• Humans
• Injections, Intramuscular
• Male
• Middle Aged
• Myocardial Revascularization (methods)
• Neovascularization, Physiologic (genetics, physiology)
• Placebos
• Proportional Hazards Models
• Risk