Topical Esmolol Hydrochloride as a Novel Treatment Modality for Diabetic Foot Ulcers: A Phase 3 Randomized Clinical Trial.

Importance: Preclinical and phase 1/2 studies with esmolol hydrochloride suggest its potential role in treatment of diabetic foot ulcers (DFUs). Objective: To study the efficacy of topical esmolol for healing of uninfected DFUs. Design, Setting, and Participants: 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. Interventions: 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT03998436; Clinical Trial Registry, India CRI Number: CTRI/2018/11/016295.

An open-label, multicenter, phase 2 study of a food enriched with docosahexaenoic acid in adults with sickle cell disease.

Sickle cell disease (SCD) induces red blood cell sickling, which causes debilitating symptoms including vaso-occlusion and inflammation. We investigated a food enriched with omega-3 fatty acids to determine its effect on certain factors: blood cell membrane fatty acid composition (including anti-inflammatory elements-docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)-and the pro-inflammatory, arachidonic acid (AA)); the inflammation biomarker, C-reactive protein (CRP); and vaso-occlusive crisis (VOC) pain. Ten adults with SCD ingested the food, daily, for 28 days. Evaluated measures included blood cell membrane fatty acid ratios (AA vs omega-3 (DHA+EPA)), CRP (mg/L) levels, and Visual Analogue Scale (VAS) scores (a VOC assessment). The food was well tolerated and led to a statistically significant CRP reduction (39%). However, changes in omega-3 fatty acid ratios and VAS scores were not significant. Overall, while the omega-3-enriched food reduced inflammation, larger, blinded studies are needed to assess its effectiveness on other measures.

Clinical Validation of Integrated Point-of-Care Devices for the Management of Non-Communicable Diseases.

Non-communicable diseases are the leading cause of death and disability across India, including in the poorest states. Effective disease management, particularly for cardiovascular diseases, requires the tracking of several biochemical and physiological parameters over an extended period of time. Currently, patients must go to diagnostic laboratories and doctors' clinics or invest in individual point-of-care devices for measuring the required parameters. The cost and inconvenience of current options lead to inconsistent monitoring, which contribute to suboptimal outcomes. Furthermore, managing multiple individual point-of-devices is challenging and helps track some parameters to the exclusion of others. To address these issues, HealthCubed, a primary care technology company, has designed integrated devices that measure blood glucose, hemoglobin, cholesterol, uric acid, blood pressure, capillary oxygen saturation and pulse rate. Here we report data from clinical studies undertaken in healthy subjects establishing the validity of an integrated device for monitoring multiple parameters.