Efficacy of Cadexomer Iodine in managing chronic wounds: Reports from a meta-analysis.

Wound management, especially chronic ones, has been a challenging task for physicians and surgeons. It has been well documented that chronic non-healing wounds offer resistance to standard antimicrobial therapy owing to the diverse biofilms and a variety of drug-resistant microflora associated with them. (1, 2)

The last decade has noted a surge in the trials on topical antimicrobials which can oppose and counteract the microbial flora in such chronic wounds, providing a favorable bed for tissue repair. Mounting evidence now highlights Cadexomer Iodine (CI), an iodophor-based topical antimicrobial, as one of the most effective drugs for chronic wounds (3,4).

Developed in the early 1980s in Sweden, Cadexomer Iodine was initially shown to be effective in the treatment of venous ulcers (5). With further research, the chronic wound healing efficacy of CI has been focused upon. Its novel role in increasing reepithelialization in wounds has been well established (6)

Available mainly in powder form, the microbeads of Cadexomer Iodine manifest their action based on a dual strategy. On contact with the wound site, the hydrophilic starch coating adsorbs wound exudates, pus, fluids, etc. The microbeads swell, finally releasing the iodine which acts as the main antimicrobial. This dual-action has helped Cadexomer Iodine in managing non-healing wounds effectively (7) while strengthening its position among the medical fraternity. With innumerable studies accumulating through the last decade in favor of Cadexomer Iodine, a systematic review analysis on the same is lacking.

To bridge this gap and to review the available scientific data supporting the use of CI in various chronic wounds including venous leg ulcers, diabetic foot, pressure ulcers, since the last 40 years, a recent elaborate meta-analysis was undertaken by Kevin Woo et al. from Queen's University, Canada (8).

This review has been published in the International Wound Journal.

Methodology

For the study design, a systematic literature search was performed using the related to cadexomer iodine and its brand names, iodine beads or iodine start AND ("wound healing" OR "chronic wound"), and no lower date limit was conducted on Embase and PubMed to identify relevant studies on 24 November 2020.

480 studies (including prospective and retrospective design) that evaluated the use of Cadexomer Iodine along with relevant wound healing outcomes in patients of any age or with any risk factors for complications were included.

Outcome measures assessed were infection, pain and wound area, and wound healing.

Data analysis highlighted some interesting results, as summarised below.

● Reduction in pain- Out of six studies that reported on pain measured using a visual analog scale (VAS) scoring following CI intervention compared with SOC; four in VLUs including significant pain reductions following 6, 9, and 8 weeks of treatment (10), and one study in PU (11), demonstrating a significant reduction in pain (P < .02) during the 8 weeks of study, was noted. In yet another study, Holloway et al. demonstrated a trend towards less pain by CI when compared with SOC in VLUs.

● Wound area reduction- Several RCTs highlighted the considerable improvements in wound area reduction in chronic wounds (VLU, DFU, and PU) after CI intervention.

Hansson et al.(12), showed a 66% reduction in ulcer area over the 12 weeks study compared to only 18% in the SOC group (P = .0127), with a significantly higher rate of healing compared to SOC (P = .0353). Hillstrom et al.(13),  demonstrated a significant reduction in VLU wound area with Cadexomer Iodine after only 1 week of treatment, and continued up to the end of the study (week 6 ). Strong and colleagues (14), also showed significant reduction in ulcer size compared to SOC at weeks 1, 2, 4, and 6 (P < .01, P < .005, P < .01, P < .02, respectively). Furthermore, the significant reduction in ulcer size by 1 and 2 weeks highlighted by Skog et al. (P<.02 and P < 0.005 respectively) equated to a 34% reduction in ulcer size by 6 weeks compared to an increase in ulcer size by 5% in the SOC group. (5) Comparable reductions in the VLU area following 8 weeks of Cadexomer Iodine treatment were also noted in a crossover trial (15) by Lindsay et al. (33.6% vs 4.2% for SOC). A 71% reduction in mean ulcer area compared to 54% in the SOC group (P < .05) over a 6-week CI intervention was noted by Laudanska and Gustavson (9). In DFU, a 53.6% median reduction in wound area and 50% reduction in wound depth were reported following Cadexomer Iodine treatment compared to baseline. (11)

● Wound healing- Several studies involving participants with VLU, DFU, and PU reported complete wound healing following Cadexomer Iodine intervention.

In VLUs, significantly more wounds were healed using CI compared to SOC across studies spanning 6 weeks, 8 weeks, and 12 weeks intervention (16). Likewise, in PUs, significantly more healing events were reported in the CI group compared to SOC in an RCT by Moberg et al. (11). Also, in an open controlled comparative study in DFU, more wounds in the CI group healed compared to the SOC comparison group. (8)

Results highlighted some interesting facts, as follows-

1. Cadexomer Iodine is the only agent that reduced total microbial load including biofilm in human clinical studies (17).

2. Wounds treated with Cadexomer Iodine are at least two times more likely to heal compared to SOC (across VLUs, DFUs, and PUs), leading to substantial cost savings in inpatient care.

3. Acknowledging the wide impact of Cadexomer Iodine in managing venous ulcers, it has been incorporated in treatment guidelines for the management of VLUs (18).

Conclusion- Affirming the fact that currently, available wound healing data demonstrated chronic wounds are more likely to heal with CI treatment compared to SOC, the research team concluded, "This systematic review of clinical studies highlights how CI treatment can manage and reduce many of these barriers, helping the Wound Healing to progress. The existing evidence for CI use in clinical practice spans almost 40 years indicating consistent successful outcomes compared to SOC. Our understanding of the efficacy of iodine, in particular, CI, against new challenges such as biofilm has reignited the interest in this intervention. Moreover, further real-world investigations of Cadexomer Iodine as part of wound bed preparation and infection management protocols would show the impact of these benefits to the patient and resources, translating observations from clinical research into clinical practice."

The above article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on Cadexomer Iodine, click HERE

References

1. Omar, A., Wright, J. B., Schultz, G., Burrell, R., & Nadworny, P. (2017). Microbial Biofilms and Chronic Wounds. Microorganisms, 5(1),9. https://doi.org/10.3390/microorganisms5010009

2. Kadam, S., Shai, S., Shahane, A., & Kaushik, K. S. (2019). Recent Advances in Non-Conventional Antimicrobial Approaches for Chronic Wound Biofilms: Have We Found the 'Chink in the Armor'?. Biomedicines, 7(2), 35. https://doi.org/10.3390/biomedicines7020035

3. Fitzgerald DJ, Renick PJ, Forrest EC, Tetens SP, Earnest DN, McMillan J, Kiedaisch BM, Shi L, Roche ED. Cadexomer iodine provides superior efficacy against bacterial wound biofilms in vitro and in vivo. Wound Repair Regen. 2017 Jan;25(1):13-24. doi: 10.1111/wrr.12497. Epub 2016 Dec 5. PMID: 27859922.

4. Roche, E. D., Woodmansey, E. J., Yang, Q., Gibson, D. J., Zhang, H., & Schultz, G. S. (2019). Cadexomer iodine effectively reduces bacterial biofilm in porcine wounds ex vivo and in vivo. International wound journal, 16(3), 674–683. https://doi.org/10.1111/iwj.13080

5. Skog, E. et al. (1983). A randomized trial comparing cadexomer iodine and standard treatment in the out-patient management of chronic venous ulcers. British Journal of Dermatology 109, 77. PMID 6344906

6. Drosou Anna, Falabella Anna, and Kirsner Robert S. (2003) Antiseptics on Wounds: An area of controversy. Wounds 159(5)149-166. http://cme.medscape.com/viewarticle/456300_2Retrieved 02/03/2009

7. Management of wound biofilm - Wounds International ; https://www.woundsinternational.com › resource

8. Woo K, Dowsett C,Costa B, Ebohon S, Woodmansey EJ, Malone M. Efficacy of topical cadexomer iodine treatment in chronic wounds: Systematic review and meta- analysis of comparative clinical trials. Int Wound J.2021;1–12. https://doi.org/10.1111/iwj.13560

9. Laudanska H, Gustavson B. In-patient treatment of chronic varicose venous ulcers. A randomized trial of cadexomer iodine versus standard dressings. J Int Med Res. 1988;16:428-435.

10. Harcup JW, Saul PA. A study of the effect of cadexomer iodine in the treatment of venous leg ulcers. Br J Clin Pract. 1986;40: 360-364.

11. Moberg S, Hoffman L, Grennert ML, Holst A. A randomized trial of cadexomer iodine in decubitus ulcers. J Am Geriatr Soc. 1983;31:462-465.

12. Hansson C. The effects of cadexomer iodine paste in the treatment of venous leg ulcers compared with hydrocolloid dressing and paraffin gauze dressing. Int J Dermatol. 1998;37:390-396.

13. Hillstrom L. Iodosorb compared to standard treatment in chronic venous leg ulcers—a multicenter study. Acta Chir Scan Suppl. 1988;544:53-56.

14. Troëng T, Skog E, Arnesjö B, Gjöres JE, Bergljung L, Gundersen JEA. A randomised multicentre trial to compare the efficacy of cadexomer iodine and standard treatment in the management of chronic venous ulcers in out patients. In: Fox J, Fisher H, eds. Cadexomer Iodine. Stuttgart: Schattauer Verlag; 1983:43-50.

15. Lindsay G, Latta D, Lyons KGB. A study in general practice of the efficacy of cadexomer iodine in venous leg ulcers treated on alternate days. Acta Ther. 1986;12:141-148.

16. Steele K, Irwin G, Dowds N. Cadexomer iodine in the management of venous leg ulcers in general practice. Practitioner.1986;230:63-68.

17. Schwarzer S, James GA, Goeres D, et al. The efficacy of topical agents used in wounds for managing chronic biofilm infections: A systematic review. J Infect. 2020;80:261-270.

18. Maessen-Visch MB, de Roos K-P. Dutch venous ulcer guideline update. Phlebology. 2014;29:153-156.