Efficacy and safety of the combination of isosorbide dinitrate spray and chitosan gel for the treatment of diabetic foot ulcers: A double-blind, randomized, clinical trial

Abstract

Aim: To evaluate whether a combination of isosorbide dinitrate spray and chitosan gel (10%) topically applied can have additive benefits for management of diabetic foot ulcers. Methods: In a randomized, placebo-controlled, double-blinded clinical trial, 68 patients were divided into four groups: Group 1: treated with chitosan gel; Group 2: isosorbide dinitrate spray; Group 3: combination of isosorbide dinitrate spray and chitosan gel; Group 4: placebo. Results: Histological analyses showed a significant regeneration in all groups (p < 0.001). On the final assessment of the ulcer, using the combination was found a wound closure percentage of 71 ± 30, 70 ± 27 using isosorbide dinitrate, 58 ± 30 with chitosan and 50 ± 16 with placebo. The number of patients who achieved complete ulcer closure was six using the combination, four with isosorbide dinitrate, three with chitosan and one with placebo. The progression in the healing process of the ulcer showed marked inmunohistochemical differences of Von Willebrand Factor, desmin, vascular endothelial growth factor-A and α-smooth muscle actin in all groups (p < 0.001), but without notable differences between them. Conclusion: The combination was better than placebo to reduce the dimensions of the ulcer, accelerate healing and increase the number of patients who achieved complete closure of the ulcer, but the combination was not better than chitosan or isosorbide dinitrate used separately.

Guidelines on use of interventions to enhance healing of chronic foot ulcers in diabetes (IWGDF 2019 update)

“…Two recent RCTs with topical Pirferidone (with potential anti‐inflammatory/antifibrotic properties) had methodological limitations; neither were blinded, results were analysed per protocol, and there was a high dropout rate in one, and an unexpectedly low healing rate in the control group in the other . Four RCTs of products designed to promote healing; Chitosan and Isosorbide dinitrate, hyaluronic acid, an acellular flowable matrix, and the proteolytic fraction from latex P1G10 provided little support for the use of these agents in clinical practice because of a small number of recruited patients, nonblinding, per protocol analysis, and/or high drop‐out rates. One RCT of a gap‐junctional protein (ACT1, a connexin43‐based gel) in patients with noninfected neuropathic ulcers showed a significantly greater reduction in mean percent ulcer area from baseline to 12 weeks but with a high rate of withdrawal of consent and protocol noncompliance …”

Therapeutic Effects of Amnion-Conjugated Chitosan-Alginate Membranes on Diabetic Wounds in an Induced Diabetic Swine Model: An In Vitro and In Vivo Study

“… 13 In a previous clinical study, CS was found to be a promising dressing material for faster wound healing in patients with chronic wounds, such as diabetic foot, pressure ulcers, and vascular ulcers. 14 15 Acylated CS fibers demonstrate a high absorbency ability of wound exudate, a faster healing time, and an increased pain relief effect in chronic wounds. 14 Our material was based on a woven CS fiber membrane that was additionally compounded with alginate to augment the absorbency of the wound exudate.…”

Effectiveness of interventions to enhance healing of chronic foot ulcers in diabetes: a systematic review

“…For completeness, studies that were previously reported in the 2016 systematic review that are not discussed in the present document have been included in the supplementary tables …”