Topical esmolol hydrochloride superior to standard of care for healing diabetic foot ulcers: Study

During the 12-week treatment phase for wound measurement and at weeks 14, 16, 20, and 24 during the follow-up phase, participants visited the investigational site once a week. Standard care included a moist wound environment, debridement, and off-loading with modified insole and shoes.

The study's primary outcome was the proportion of wound closure within 12-week in Esmolol + SoC and SoC only groups. The secondary outcomes were a proportion of participants achieving target ulcer closure (24 weeks) and time to ulcer closure during the treatment phase. Target ulcer closure was defined as 100% re-epithelialization, confirmed on two consecutive site visits two weeks apart. All analyses were conducted for intention-to-treat (ITT), i.e., safety evaluable population.

The screening of 251 participants was done, and 176 were randomized to the three groups.

The researchers found the following:

• The proportion of participants who achieved target ulcer closure within 12 weeks was 60·3% participants in Esmolol + SoC group compared to 41·7% participants in SoC only group (OR = 2·126).
• The proportion of target ulcer closure by the end of the study (week 24) was achieved in 44 of 77·2% participants in the Esmolol + SoC group and 55·6% participants in the SoC only group (OR = 2·708).
• The mean time for ulcer closure was similar (74·3 days for Esmolol + SoC group and 72·5 days for SoC only group).
• The Esmolol + SoC group showed a significant advantage over SoC in participants with BMI>25 kg/m2, high HbA1c, longer ulcer duration, hemoglobin<11 g/dl, low eGFR, and ulcers that did not achieve 50% area reduction within initial four weeks of treatment.
• The percent ulcer area reduction from end-of-treatment to end-of-study was 60·7% for Esmolol + SoC group compared to a negligible decrease of 2·7% in the SoC-only group.

To conclude, esmolol hydrochloride 14% topical gel treated diabetic foot ulcers much better than the standard of care (SoC) and did not cause significant drug-related safety issues.

Reference:

Rastogi A et al. Novel topical esmolol hydrochloride for diabetic foot ulcer: phase 3, randomised, double-blind, placebo-controlled, multi-centre study. Presented at the 58th European Association for the Study of Diabetes (EASD) Annual Meeting 2022 on 20 September 2022.