OBJECTIVE -To study the healing effect of recombinant human epidermal growth factor (hEGF) on diabetic foot ulcers. RESEARCH DESIGN AND METHODS-A total of 127 consecutive patients were screened and 61 diabetic subjects were recruited into this double-blind randomized controlled study. Predetermined criteria were used for diagnosis and classification of the diabetic wound. The patients were randomized into three groups. All patients attended our Diabetes Ambulatory Care Center every other week for joint consultation with the diabetologist and the podiatrist. Group 1 (control) was treated with Actovegin 5% cream (Actovegin), group 2 with Actovegin plus 0.02% (wt/wt) hEGF, and group 3 with Actovegin plus 0.04% (wt/wt) hEGF. The study end point was the complete closure of the wound. Failure to heal was arbitrarily defined as incomplete healing after 12 weeks.RESULTS -Final data were obtained from 61 patients randomly assigned into three groups. The mean ages of the patients, wound sizes, wound duration, metabolic measurements, and comorbidities were comparable within groups, except that group 3 had more female patients. Mean follow-up for the patients was 24 weeks. Data were cutoff at 12 weeks, and results were analyzed by intention to treat. After 12 weeks, in group 1 (control) eight patients had complete healing, two patients underwent toe amputation, and nine had nonhealing ulcers. In group 2 (0.02% [wt/wt] hEGF) 12 patients experienced wound healing, 2 had toe amputations, and 7 had nonhealing ulcers. Some 20 of 21 patients in group 3 (0.04% [wt/wt] hEGF) showed complete wound healing. Healing rates were 42.10, 57.14, and 95% for the control, 0.02% (wt/wt) hEGF, and 0.04% (wt/wt) hEGF groups, respectively. Kaplan-Meier survival analysis suggested that application of cream with 0.04% (wt/wt) hEGF caused more ulcers to heal by 12 weeks and increased the rate of healing compared with the other treatments (log-rank test, P ϭ 0.0003).CONCLUSIONS -Our data support the contention that application of hEGF-containing cream, in addition to good foot care from a multidisciplinary team, significantly enhances diabetic foot ulcer wound healing and reduces the healing time. Diabetes Care 26:1856 -1861, 2003D iabetic foot ulcer is a major complication of diabetes. People with diabetes show a 5-to 50-fold higher risk of nontraumatic amputation compared with individuals who do not suffer from diabetes (1). Between 1996 and 1998, diabetic patients accounted for 47% of all the lower-limb amputations performed in our hospital (M.W.T., K.-M.L., G.K., unpublished data), comparable to published data (2). The major risk factor leading to diabetic foot ulcer is poor diabetes control, which results in neuropathic and vascular changes. In general, diabetic foot ulcers are difficult to heal and frequently lead to amputation if complicated by infection and gangrene. Several new treatment modalities, such as exposure to an oxygen chamber, the use of platelet-derived growth factor (PDGF), and the application of various local dressings, have p...