Effect of Fibroblast Growth Factor NV1FGF on Amputation and Death: A Randomised Placebo-Controlled Trial of Gene Therapy in Critical Limb Ischaemia

Study Questions:

What is the impact of nonviral 1 fibroblast growth factor (NV1FGF) injections on amputation-free survival in patients with severe peripheral vascular disease?


The authors randomized 525 patients with critical limb ischemia unsuitable for revascularization to either NV1FGF 0.2 mg/ml or matching placebo. All patients had ischemic ulcer in their legs or minor skin gangrene and met hemodynamic criteria (ankle pressure <70 mm Hg or a toe pressure <50 mm Hg, or both, or a transcutaneous oxygen pressure <30 mm Hg on the treated leg). Randomization was stratified by diabetes status and country. Patients received eight intramuscular injections of their assigned treatment in the index leg on days 1, 15, 29, and 43. The primary endpoint was time to major amputation or death at 1 year.


The study assigned 259 patients to NV1FGF and 266 patients to placebo. The mean age of the cohort was 70 years and 53% were diabetic. There was no difference in the primary endpoint (33% vs. 36%; hazard ratio, 1.11; 95% confidence interval, 0.83-1.49; p = 0.48) or components of the primary endpoint between treatment groups. There was no difference in side effects between the two groups.


The authors concluded that NV1FGF is ineffective for reduction of amputation or death in patients with critical limb ischemia.


This study adds to the list of failed gene strategies that have been evaluated for treatment of critical limb ischemia. Better utilization of primary and secondary preventive therapies upstream may be a more effective strategy at reducing the mortality and morbidity associated with advanced peripheral arterial disease, and remains woefully inadequate in this patient population. Only 62% of patients in this trial were on statins, and it is likely that the number is even lower among patients treated outside the trial setting. Public reporting and payment incentives have been highly successful at improving use of evidence-based therapy in patients with cardiac disease, and these strategies need to be applied to patients with peripheral arterial disease.

Keywords: Heart Diseases, Gangrene, Toes, Lower Extremity, Leg, Hemodynamics

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