医学
艾司洛尔
糖尿病足
随机对照试验
人口
糖尿病足溃疡
临床试验
内科学
麻醉
外科
糖尿病
血压
心率
环境卫生
内分泌学
作者
Ashu Rastogi,Sudhir A Kulkarni,Sanjay Agarwal,Murtaza Akhtar,Sachin Arsule,Sudhir Bhamre,Deepak Bhosle,Sanjay Desai,Manisha Deshmukh,K V Giriraja,Jagannath Jagannath,Reema Yuvraj Kashiva,Rajesh Kesavan,Deepak Khandelwal,Sanjay Kolte,Srikanth Kongara,Anil Kumar Darivemula,C Madhusudan,Mohammad Asif Haji Pyare Saheb Qureshi,Muthu Ramu,Gunvant Rathod,Sadasiva Rao Yalamanchi,Shobhit Shakya,Prathvi Shetty,Sudagar Singh,Supreet K Deshpande,Vijay Viswanathan,Ambika G Unnikrishnan
出处
期刊:PubMed
日期:2023-05-01
卷期号:6 (5): e2311509-e2311509
标识
DOI:10.1001/jamanetworkopen.2023.11509
摘要
Preclinical and phase 1/2 studies with esmolol hydrochloride suggest its potential role in treatment of diabetic foot ulcers (DFUs).To study the efficacy of topical esmolol for healing of uninfected DFUs.A randomized, double-blind, multicenter, phase 3 clinical trial was conducted from December 26, 2018, to August 19, 2020, at 27 referral centers across India. Participants included adults with DFUs.Participants were randomized after a run-in phase (1 week) to receive esmolol, 14%, gel with standard of care (SoC), SoC only, or vehicle with SoC (3:3:1 proportion) for 12 weeks (treatment phase) and followed up subsequently until week 24.The primary outcome was the proportion of wound closure within the 12-week treatment phase in the esmolol with SoC and SoC only groups. Analysis was conducted using an intention-to-treat safety evaluable population, full analysis set or efficacy-evaluable population, and per-protocol population comparing the esmolol plus SoC and SoC only treatment groups.In the study, 176 participants (122 men [69.3%]; mean [SD] age, 56.4 [9.0] years; mean [SD] hemoglobin A1c level, 8.6% [1.6%]) with DFUs classified as University of Texas Diabetic Wound Classification system grade IA and IC (mean [SD] ulcer area, 4.7 [2.9] cm2) were randomized to the 3 groups. A total of 140 participants were analyzed for efficacy. The proportion of participants in the esmolol with SoC group who achieved target ulcer closure within 12 weeks was 41 of 68 (60.3%) compared with 30 of 72 (41.7%) participants in the SoC only group (odds ratio [OR], 2.13; 95% CI, 1.08-4.17; P = .03). A total of 120 participants completed the end of study visit which were analyzed. Target ulcer closure by the end of the study (week 24) was achieved in 44 of 57 (77.2%) participants in the esmolol with SoC group and 35 of 63 (55.6%) participants in the SoC only group (OR, 2.71; 95% CI, 1.22-5.99; P = .01). The median time for ulcer closure was 85 days for the esmolol with SoC group and was not estimable for SoC only group. Significant benefits of Esmolol with SoC were seen in patients with factors that impede the healing of DFU. Treatment-emergent adverse events were noted in 18.8% of the participants, but most (87.3%) of these events were not attributable to the study drug.In this multicenter, randomized, double-blind clinical trial, the addition of esmolol to SoC was shown to significantly improve the healing of DFUs. With these results, topical esmolol may be an appropriate addition to SoC for treating DFUs.ClinicalTrials.gov Identifier: NCT03998436; Clinical Trial Registry, India CRI Number: CTRI/2018/11/016295.