Efficacy and safety of topical phenytoin cream in diabetic foot ulcers: A randomized, open-label, parallel, and proof-of-concept study.

Background: Diabetic foot ulcers (DFUs) are a severe diabetes complication, often leading to amputations. Despite medical advancements, no standard treatment exists. Conventional care is insufficient, prompting research into new therapies. Aims and Objectives: Phenytoin, an antiepileptic drug, has shown potential in wound healing by stimulating fibroblast proliferation. This study evaluated the efficacy and safety of topical phenytoin cream versus standard care for DFUs. Materials and Methods: This randomized, open-label trial was conducted at a tertiary hospital in India. Adults with diabetes and full-thickness lower extremity ulcers (Grade IA or II, University of Texas Classification) were randomized 1:1 to receive either topical phenytoin 1% cream or saline dressing daily for 8 weeks. The primary outcome was complete ulcer healing at 8 weeks. Secondary outcomes were healing time, ulcer size reduction, and adverse events. The primary outcome was analysed using the Chi-square test for independence, while secondary outcomes, namely time to wound closure, the percentage reduction in ulcer surface area and incidence of adverse events were analysed using the log-rank test, Mann-Whitney U test and Chi-square test respectively. Results: Among 28 participants, two were lost to follow-up. Healing rates were 23% (phenytoin) vs. 53% (saline) (p=0.102). Median healing time was 8 weeks in both groups (p=0.142). Ulcer size reduction was greater with saline (89.19% ± 17.33%) than phenytoin (56.51% ± 46.11%; p=0.037). Adverse events were fewer with phenytoin (p=0.431). Conclusion: Topical phenytoin was safe but not superior. Larger trials are needed to confirm its role in DFU treatment.