Treatment with <scp>LL</scp>‐37 is safe and effective in enhancing healing of hard‐to‐heal venous leg ulcers: a randomized, placebo‐controlled clinical trial

<jats:title>Abstract</jats:title><jats:p>Venous leg ulcers (<jats:styled-content style="fixed-case">VLUs</jats:styled-content>) are one of the most prevalent types of chronic wounds. The aim of this study was to determine the safety and dose–response efficacy of the human synthetic peptide <jats:styled-content style="fixed-case">LL</jats:styled-content>‐37 in the treatment of hard‐to‐heal <jats:styled-content style="fixed-case">VLUs</jats:styled-content>. This first‐in‐man trial included 34 participants with <jats:styled-content style="fixed-case">VLUs</jats:styled-content> and comprised a 3‐week, open‐label, run‐in period on placebo, followed by a 4‐week randomized double‐blind treatment phase with twice weekly applications of <jats:styled-content style="fixed-case">LL</jats:styled-content>‐37 (0.5, 1.6, or 3.2 mg/mL) or placebo, and a 4‐week follow‐up. The healing rate constants for 0.5 and 1.6 mg/mL of <jats:styled-content style="fixed-case">LL</jats:styled-content>‐37 were approximately six‐ and threefold higher than for placebo (<jats:italic>p</jats:italic> = 0.003 for 0.5 mg/mL and <jats:italic>p</jats:italic> = 0.088 for 1.6 mg/mL). Square‐root transformed wound area data showed improved healing for the 0.5 and 1.6 mg/mL dose groups compared with pretreatment values (<jats:italic>p</jats:italic> < 0.001 and <jats:italic>p</jats:italic> = 0.011, respectively). Consistently, treatment with the two lower doses markedly decreased the mean ulcer area (68% for 0.5 mg/mL and 50% for 1.6 mg/mL groups). No difference in healing was observed between the groups receiving 3.2 mg/mL of <jats:styled-content style="fixed-case">LL</jats:styled-content>‐37 and placebo. There were no safety concerns regarding local or systemic adverse events. In conclusion, topical treatment with <jats:styled-content style="fixed-case">LL</jats:styled-content>‐37 for chronic leg ulcers was safe and well tolerated with the marked effect on healing predictors at the two lower doses warranting further investigations.</jats:p>