Intralesional injections of Citoprot‐P^® (recombinant human epidermal growth factor) in advanced diabetic foot ulcers with risk of amputation

Abstract

To investigate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) in advanced diabetic foot ulcers (DFU) A double-blind trial was carried out to test two rhEGF dose levels in type 1 or 2 diabetes patients with Wagner's grade 3 or 4 ulcers, with high risk of amputation. Subjects were randomised to receive 75 (group I) or 25 mug (group II) rhEGF through intralesional injections, three times per week for 5-8 weeks together with standardised good wound care. Endpoints were granulation tissue formation, complete healing and need of amputation. Safety was assessed by clinical adverse events (AEs) and laboratory evaluations. Forty-one patients were included. After 5-8 weeks of treatment, 83% patients in the higher dose group and 61% in group II achieved useful granulation tissue covering more than 98% of the wound area. At long-term assessment, 13 (56.5%) patients healed in group I and 9 (50%) in group II. The mean time to complete healing in group I was 20.6 weeks (95% CI: 17.0-24.2) and 19.5 weeks (16.3-22.7) in group II. After 1-year follow-up, only one patient relapsed. Amputation was not necessary in 65% and 66.7% of groups I and II, respectively. The AEs rates were similar. The most frequent were sepsis (33%), burning sensation (29%), tremors, chills and local pain (25% each). rhEGF local injection enhances advanced DFU healing and reduces the risk of major amputation. No dose dependency was observed.

Intralesional epidermal growth factor therapy fordiabetic foot ulcers: an evaluation of 15 cases

“…The authors reported that a potential amputation was prevented in 17 (58%) patients, and underlined the efficacy of intralesional EGF therapy in decreasing amputation rates (7). In their 2007 study comparing intralesional EGF doses of 75 µg (n: 23) and 25 µg (n: 18), Fernandez-Montequin et al reported faster and more frequent formation of granulation tissue under a higher dose of EGF therapy (83% and 61%, respectively) (8).…”

A fragment of secreted Hsp90α carries properties that enable it to accelerate effectively both acute and diabetic wound healing in mice

“…Intriguingly, however, even in the presence of TGF-β3 ( Figure 7A, far right column), F-5 remained equally effective on stimulation of migration of all 3 cell types. Quantitation of these results is shown in Figure 7B (bars [10][11][12][13][14][15]. This second unique property of F-5 provides another explanation for why F-5 heals wounds faster than becaplermin.…”

“…Since the first report of the EGF clinical trial on wound healing in 1989 (8), more than a dozen growth factor trials have been conducted. The list includes (a) EGF on partialthickness wounds of skin grafts (8), on traumatic corneal epithelial defects (9), on tympanic membrane with chronic perforation (10), and on advanced diabetic foot ulcers (11,12); (b) bFGF on partialthickness burn wounds of children (13), on second-degree burns (14), and on diabetic ulcers (15); (c) acidic FGF on partial-thickness burns and skin graft donor sites (16); (d) GM-CSF plus bFGF on pressure ulcers (17); and (e) PDGF-BB on chronic pressure and diabetic ulcers (18)(19)(20)(21)(22). Despite the fact that most of these doubleblinded trials reported promising clinical efficacies in humans, only the human recombinant PDGF-BB has received US FDA approval for treatment of limb diabetic ulcers (Regranex, becaplermin gel 0.01%, Ortho-McNeil Pharmaceutical) (20).…”

Type 2 Diabetes Mellitus (T2DM): Biological Overview from Pathways to Organelles and its Translation toward a Torpid Wound Healing Process

“…All the lesions were chronic, complex and recalcitrant to heal, staged as grades III or IV of the Wagner's scale. The efficacy showed in this type of wounds [138] paved the way for a solid clinical development, which successfully culminated with a multicenter, double-blinded, placebo-controlled phase III clinical trial in which an unprecedented efficacy and safety profile were reported for high-grade ulcers [139][140][141][142][143][144]. Ongoing studies from our group (Jorge Berlanga-Acosta, unpublished data) have shown that locally infiltrated EGF is able to trigger acute and long term gene responses.…”