Intra-lesional injections of recombinant human epidermal growth factor promote granulation and healing in advanced diabetic foot ulcers: multicenter, randomised, placebo-controlled, double-blind study

A multicenter, double-blind, placebo-controlled trial was carried out to evaluate the intra-lesional infiltration of recombinant epidermal growth factor (EGF) in Wagner's grade 3 or 4 diabetic foot ulcers (DFUs). Subjects (149) were randomised to receive EGF (75 or 25 mu g) or placebo, three times per week for 8 weeks and standard good wound care. The main endpoint was granulation tissue covering >= 50% of the ulcer at 2 weeks. It was achieved by 19/48 controls versus 44/53 in the 75 mu g group [odds ratio (OR): 7.5; 95% confidence interval (CI): 2.9-18.9] and 34/48 in the 25 mu g group (OR: 3.7; 1.6-8.7). Secondary outcome variables such as end-of-treatment complete granulation response (28/48 controls, 46/53 with 75 mu g and 34/48 with 25 mu g EGF), time-to-complete response (controls: 5 weeks; both EGF dose groups: 3 weeks), and wound closure after follow-up (25/48 controls, 40/53 with 75 mu g and 25/48 with 25 mu g EGF) were also treatment dependent. Multivariate analyses yielded that they were significantly enhanced by 75 mu g EGF treatment and neuropathic versus ischemic ulcers. Most adverse events were mild and no drug-related severe adverse reactions were reported. It was concluded that recombinant human EGF (rhEGF) local injections offer a favourable risk-benefit balance in patients with advanced DFU.