Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial.

Publisher: Blackwell Science Country of Publication: United States NLM ID: 9310939 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-475X (Electronic) Linking ISSN: 10671927 NLM ISO Abbreviation: Wound Repair Regen Subsets: MEDLINE

Publication: <2010-> : Malden, MA : Blackwell Science
Original Publication: St. Louis, MO : Mosby, c1993-

Leg Ulcer*/drug therapy ; Varicose Ulcer*/drug therapy; Aged ; Double-Blind Method ; Humans ; Prospective Studies ; Treatment Outcome ; Wound Healing

Many patients with venous leg ulcers do not reach complete healing with compression treatment alone, which is current standard care. This clinical trial HEAL LL-37 was a phase IIb double-blind, randomized, placebo-controlled study, with the aim to evaluate the efficacy and safety of a new drug LL-37 for topical administration, in combination with compression therapy, in 148 patients suffering from hard-to-heal venous leg ulcers. The study had three arms, consisting of two groups treated with LL-37 at concentrations of 0.5 or 1.6 mg/mL, and a placebo cohort. Patients had a mean age of 67.6 years, a median ulcer duration of 20.3 months, and a mean wound size at the time of randomization of 11.6 cm ² . Efficacy analysis performed on the full study population did not identify any significant improvement in healing in patients treated with LL-37 as compared with the placebo. In contrast, a post hoc analysis revealed statistically significant improvement with LL-37 treatment in several interrelated healing parameters in the subgroup of patients with large target wounds (a wound area of at least 10 cm ² at randomization), which is a known negative prognostic factor for healing. The study drug was well tolerated and safe in both dose strengths. In summary, this clinical trial did not detect any significant differences in healing of venous lower leg ulcers in the entire study cohort comparing patients treated with LL-37 versus placebo. A subgroup analysis provided an interesting observation that LL-37 could offer a treatment benefit in patients with large ulcers, exigently warranting a further study adequately powered to statistically assess the treatment outcome in this patient group.
(© 2021 Promore Pharma AB. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

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Keywords: LL-37; phase II clinical trial; venous leg ulcers; wound healing

Date Created: 20211023 Date Completed: 20220131 Latest Revision: 20220731

20231215

PMC9298190

10.1111/wrr.12977

34687253