Temple University School of Podiatric Medicine Journal Review Club
Editor's note: This post is part of the Temple University School of Podiatric Medicine (TUSPM) journal review club blog series. In each blog post, a TUSPM student will review a journal article relevant to wound management and related topics and provide their evaluation of the clinical research therein.
Article Title: Efficacy of Cadexomer Iodine in the Treatment of Chronic Ulcers: A Randomized, Multicenter, Controlled Trial
Authors: Radhakkrishnan R, Kethavath SN, Sangavarapu SM, Kanjarla P, Dexadine Study Group
Journal: Wounds. 2019;31(3):85-90
Reviewed by: Elizabeth Connolly, class of 2021, Temple University School of Podiatric Medicine
When iodine-based preparations contact wound exudate, they release free iodine and add to the antiseptic needs of wound healing. With multidrug-resistant bacteria on the rise, a preparation of cadexomer with iodine has been shown to reduce the bacterial load while absorbing fluid exudate (6ml/g of cadexomer iodine), removing pus, facilitating de-sloughing, and maintaining a moist environment. However, iodine can be absorbed systemically and can affect metabolic functioning, so the benefits of this treatment need to outweigh the risks before this regimen is used as protocol for chronic ulcers in immunocompromised individuals.
Controlled trials within this investigation compared two main formulations of cadexomer iodine and standard care of treatment with respect to chronic ulcer healing. The efficacy, safety, and adverse reactions of the treatments, the demographic features and comorbidities of the patients, and the types of ulcers treated were all factors evaluated when recording the data. The patient population (124 total) was recorded from eight cities across India, with an average age of participants of 47.6 ± 11.7 years. The participants were mostly middle-aged men (63%). Strict inclusion criteria were a single venous leg ulcer, diabetic foot ulcer, or pressure ulcer with an adequate blood supply (ankle-brachial index ≥0.8), a duration of at least four weeks, and a size ranging from 2 to 10cm2 (5.6cm2 average).
Exclusion criteria were as follows: uncontrolled hyperglycemia (hemoglobin A1c ≥9), renal failure (creatinine >3.0 mg/dl), poor nutritional status (albumin <3.0 g/dl; protein <6.5 g/dl), history of thyroid disease, human immunodeficiency virus–positive status, use of any type of immunosuppressive agents, or failure to complete treatment. The patients were randomly divided into the three following treatment groups: 0.9% cadexomer iodine ointment with standard care, 0.9% cadexomer iodine powder with standard care, and standard care alone. Participants receiving standard care had varied treatments according to the nature of their wounds. These treatments included offloading, such as with crutches, orthopedic shoes, wheelchairs, and cast walkers, and compression bandaging.
All standard care required consistent cleaning of the wound with sterile saline and over non-adherent absorbent gauze. However, these patients also followed a metabolic control regimen and received treatment of comorbidities that, unfortunately, was not clearly described. Given the lack of detail reported for this type of treatment, one could wonder whether these variables added to inferior or improved healing times. For example, if a patient underwent a revascularization procedure, this would affect healing time and alter the efficacy of the trial. However, because all three groups followed a metabolic control regimen, one could argue that this discrepancy was accounted for within the data. Treatment efficacy parameters focused on the three main factors of the ulcer. The reduction of ulcer size was recorded at the ninth visit and was calculated by multiplying the greatest width by the greatest length. The mean change in ulcer size was recorded on the 12th week and was compared with the baseline.
In addition, as for the baseline, the wound evaluation score was created by five wound parameters of edema, pain, exudate, erythema, and pus. The severity of the wound evaluation score was then measured on a scale from 0 to 3: absent (0), mild (1), moderate (2), and severe (3). The sample size of the study, with more than 36 participants in each group, was large enough to be statistically relevant.
All wounds were reduced in size in all three treatment groups. Standard care alone reduced wound size by 34%, whereas the group receiving the cadexomer iodine ointment had a reduction in wound size of 62% at 12 weeks. Based on the controlled trial parameters, a higher percentage of wound healing and reduction in wound size was achieved with both cadexomer iodine preparations than with standard care alone. The group receiving cadexomer iodine ointment had a maximum reduction of ulcer size at 94%, and participants treated with cadexomer iodine powder had a maximum reduction of ulcer size at 90.4%, compared with standard care, which was associated with a 67.8% average maximum reduction of ulcer size. There were few side effects compared with healing success, with 17 patients reporting 27 adverse reactions overall.
Eight adverse reactions were reported by seven patients in the cadexomer iodine ointment group, seven adverse events were reported by three participants in the cadexomer iodine powder group, and 12 adverse were reported in seven patients in the standard care–alone group. All adverse events are considered mild to moderate except in one participant, who received the ointment. However, this event was believed to be related to another illness and not to the treatment. All adverse events in this study were resolved uneventfully. Overall, based on the results of the study, the cadexomer iodine ointment is very easy to apply and is less dependent on wound moisture as compared with the powder, and it had slightly better healing rates.
The limitations of the population accepted into the study may not be representative of the limitations of the patients who have these chronic ulcers because of the comorbidities that were excluded. It is unlikely for a person to have controlled diabetes with a chronic ulcer and no other underlying disorders. A future study conducted in patients with chronic ulcers and other comorbidities would better represent those patients who would be likely to use this cadexomer iodine product. However, this would create additional issues in conducting a non-biased study.
About the Author
Elizabeth Connolly was a pre-medical biology major at Northeastern University. She is now a third year student at Temple University School of Podiatric Medicine. She has volunteered in South Africa podiatric clinics and operating rooms, as well as in US-based homeless shelters, which helped to encourage her passion for podiatry. Dr. James McGuire is the director of the Leonard S. Abrams Center for Advanced Wound Healing and an associate professor of the Department of Podiatric Medicine and Orthopedics at the Temple University School of Podiatric Medicine in Philadelphia.
The views and opinions expressed in this blog are solely those of the author, and do not represent the views of WoundSource, HMP Global, its affiliates, or subsidiary companies.