A Systematic Review of Clinical Efficacy Associated with use of Protease-Modulating Interventions with Diabetic Foot Ulcer or Venous Leg Ulcer

OBJECTIVES: Diabetic foot ulcers (DFUs) or leg ulcers (LUs) of venous, arterial or mixed origin can cause a considerable burden to a patient and healthcare provider, taking a long time to heal and requiring frequent interventions. Dressings are a mainstay of treatment with countless options for a Healthcare Provider. Protease-modulating matrix (PMM) interventions are an alternative to basic or other advanced dressings. A systematic review was undertaken to assess the clinical effectiveness of PMM interventions for DFUs and LUs. METHODS: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. An online database search, and consultation with experts and manufacturers identified the literature. Databases searched included: Centre Reviews and Dissemination (CRD) York Database, Cochrane Library, Medline (PubMed), National Institute for Health and Clinical Excellence Evidence Search, Science Direct/Scopus. Two researchers performed data extraction with a third consulted in case of any discrepancies. A narrative synthesis of results and critical appraisal of included studies was performed. RESULTS: A total of 283 records were identified by literature searching. After initial screening of titles and abstracts, 215 full text articles were judged against pre-defined inclusion and exclusion criteria. Six randomised controlled trials and 2 observational studies were included in the review. A total of 1310 patients were included in this study. The three VLU RCTs included a total of 377 patients, and the DFU studies included 933 patients. Healing was the most frequently reported outcome, followed by wound area reduction. A meta-analysis was not possible given the heterogeneity of the included studies. CONCLUSIONS: This review provides some evidence that PMM interventions have a clinical benefit on wound healing outcomes; however, there were several methodological issues with the studies included. New evidence shows promising results for the treatment of DFUs involving protease modulation by sucrose octasulfate dressings.