Topical esmolol 14% hydrochloride plus standard of care treatment can achieve more wound closure for diabetic foot ulcers compared with standard of care treatment alone, according to research published in Diabetes and Endocrinology.
Researchers conducted randomized, double-blind phase 3 clinical trial from 2018 and 2020 that included 176 participants (mean age, 56.4 years; 69.3% men) with grade 1A and 1C diabetic foot ulcers who were treated at 1 of 27 clinical centers. The team randomly assigned study participants to treatment with esmolol 14% gel with standard of care, standard of care only, or vehicle with standard of care for 12 weeks, but performed follow up until week 24. The study’s primary outcome was to determine the proportion of wound closure within the 12-week treatment phase in the esmolol with standard of care and standard of care only groups.
Among 140 participants undergoing an efficacy analysis in the topical esmolol and standard of care groups, 60.3% of participants treated with esmolol plus standard of care reached target ulcer closure within 12 weeks compared with 41.7% of patients undergoing standard of care therapy alone (OR, 2.13; 95% CI, 1.08-4.17; P =.03).
At week 24, an analysis of 120 participants revealed wound closure in 77.2% of participants treated with topical esmolol compared with 55.6% of individuals who received standard of care therapy (OR, 2.71; 95% CI, 1.22-5.99; P =.01).
Among patients treated with topical esmolol, the median time for wound closure was 85 days. More ulcers experienced closure with topical esmolol treatment in patients with weight greater than 80 kg (OR, 4.04; 95% CI, 1.07-15.27; P =.04) and body mass index greater than 25 (OR, 2.72; 95% CI, 1.08-6.79; P =.03) compared with the standard of care treatment alone.
In the intent-to-treat population, 18.8% of participants reported treatment-emergent adverse events, but the investigators determined that none were drug-related.
The researchers highlight the importance of topical esmolol’s ability to treat diabetic foot ulcers in patients who may be most susceptible to impaired wound closure.
“An increased weight and body mass index are known to exert pressure on plantar ulcers and are key factors delaying wound healing.” The study authors explain. “The esmolol with [standard of care] group showed significantly greater wound closure in people with characteristics that impair wound healing, including those with peripheral arterial disease, anemia, and nephropathy compared with [standard of care] alone.”
Failure to achieve the targeted sample size due to COVID-19-related concerns is an acknowledged limitation to the research.
Disclosure: This research was supported by NovaLead Pharma Pvt Ltd. Some study authors declared affiliations with biotech, pharmaceutical and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Rastogi A, Kulkarni SA, Agarwal S, et al. Topical esmolol hydrochloride as a novel treatment modality for diabetic foot ulcers: a phase 3 randomized clinical trial. JAMA Netw Open. Published online May 1, 2023. doi:10.1001/jamanetworkopen.2023.11509