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

This was the first randomized clinical trial to evaluate the efficacy of the LL-37 peptide as a topical treatment for chronic venous ulcers in humans. The double-blind, placebo-controlled study included 34 patients with venous leg ulcers that had not healed for at least 6 months despite adequate compression therapy.

Participants were randomized to receive topical LL-37 at three different doses (0.5, 1.6, or 3.2 mg/mL) or vehicle placebo, applied directly to the wound three times per week for 4 weeks. The primary endpoint was healing rate measured by digital planimetry.

The results were remarkable: healing rates with LL-37 were up to six times higher than those observed with placebo. The group receiving the intermediate dose of 1.6 mg/mL showed the best response, with significant reduction in wound area throughout treatment. The safety profile was excellent — the topical treatment was well tolerated, with no serious adverse events related to the peptide.

This study translated into clinical practice the preclinical findings from over a decade of research on the role of LL-37 in wound healing. The demonstration of safety and efficacy in humans with refractory ulcers represents an important milestone, validating the approach of using endogenous antimicrobial peptides as therapeutic agents for chronic wounds.