(CR-008) Comparison of Safety Profile of Venous Stasis and Diabetic Foot Ulcers in Clinical Trials at a Tertiary, Safety Net Hospital.

Marina Malikova, PhD, MACI, MBA – Research Director, Surgical Research, Boston Medical Center; Vitaliy Volansky, DPM – Assistant Professor, Podiatry, Boston Medical Center

Introduction: Currently, leg ulcers have increased interest for research due to high financial burden on healthcare systems to manage chronic wounds.^1,2 It is necessary to maintain balance between efficient study conduct and patient safety.³ The purposes of this study is to evaluate what adverse events are most common between diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) populations, and which patients are more susceptible to having adverse events in order to develop risk and safety mitigation strategies for wound care clinical trials.

Methods:

An audit of prospective, randomized wound care clinical trials was performed.  Overall, 223 adverse events were assessed in 261 enrolled subjects. The rate/patterns of serious adverse events (SAEs), which required hospitalization/intervention; and non-serious adverse events (AEs) were assessed and compared between two ulcer indications. The expectedness based on known safety profile of experimental drug/device and the relatedness to study products/procedures to the adverse events were assessed.

Results:

A comparison of SAEs incidence rate between DFU and VLU studies showed an average of 0.13 SAEs and 0.09 SAEs per patient, respectively. The most common categories were infections, both of the wound and non-wound locations, and worsening of pre-existing conditions. The rate of non-serious adverse events (AEs) was similar at 0.78 and 0.71 AEs/patient for DFU and VLU studies, respectively. Overall, the DFU group was noted to have a 30% higher incidence of SAEs; and a 7% higher incidence of AEs.  The SAEs (34%) and AEs (51%) in the DFU indication were more expected as compared to VLUs (AEs 9.8% vs. SAEs 4.5%). Overall,  relatedness of the adverse events to study products were 0% “related” and 6.7% “possibly related” in the DFU group and 5.4% “related” and 4.2% “possibly related” in the VLU group.

Discussion:

Overall, DFU trials had higher rate of adverse events, mostly attributed to exacerbation of pre-existing conditions rather than study products/procedures, as compared to VLU studies.  

When conducting clinical trials, an understanding/managing co-morbidities, as well as adverse events can contribute to development of more effective safety monitoring plans and risk mitigation strategies for wound care trials with different etiology.

Trademarked Items:

References: 1. Leg Ulcers Clinical Trials.Gov. Clinical Trials. Retrieved June 9, 2023, from https://clinicaltrials.gov/ct2/results?cond=leg+ulcers&term=&cntry=&state=&city=&dist=
2. Chan, B., Cadarette, S., Wodchis, W., Wong, J., Mittmann, N., & Krahn, M. (2017). Cost-of-illness studies in chronic ulcers: a systematic review. Journal of wound care, 26(sup4), S4–S14. https://doi.org/10.12968/jowc.2017.26.Sup4.S4
3. Beyene R.T., Derryberry S.L., Barbul A. The Effect of Comorbidities on Wound Healing. Surg Clin North Am. 2020 Aug;100(4):695-705. doi: 10.1016/j.suc.2020.05.002. Epub 2020 Jun 17. PMID: 32681870.