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This study sought to evaluate the clinical benefit of topical activated protein C (<jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content>) on chronic lower leg ulcers in patients with diabetes. Twelve patients were randomly assigned to receive either <jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content> (<jats:italic>N<\/jats:italic> = 6) or physiological saline (placebo; <jats:italic>N<\/jats:italic> = 6) in a randomised, placebo\u2010controlled, double\u2010blind pilot clinical trial. Treatment was administered topically, twice weekly for 6 weeks with final follow\u2010up at 20 weeks. Wound area was significantly reduced to 34\u00b78 \u00b1 16\u00b74% of week 0 levels at 20 weeks in <jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content>\u2010treated wounds (<jats:italic>p<\/jats:italic> = 0\u00b701). At 20 weeks, three <jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content>\u2010treated wounds had completely healed, compared to one saline\u2010treated wound. Full\u2010thickness wound edge skin biopsies showed reduced inflammatory cell infiltration and increased vascular proliferation following <jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content> treatment. Patient stress scores were also significantly reduced following <jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content> treatment (<jats:italic>p<\/jats:italic> &lt; 0\u00b705), demonstrating improved patient quality of life as assessed by the Cardiff Wound Impact Questionnaire. This pilot trial suggests that <jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content> is a safe topical agent for healing chronic lower leg ulcers in patients with diabetes and provides supporting evidence for a larger clinical trial.<\/jats:p>","DOI":"10.1111\/iwj.12125","type":"journal-article","created":{"date-parts":[[2013,7,15]],"date-time":"2013-07-15T09:33:23Z","timestamp":1373880803000},"page":"422-427","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Treatment of chronic diabetic lower leg ulcers with activated protein C: a randomised placebo\u2010controlled, double\u2010blind pilot clinical trial"],"prefix":"10.1111","volume":"12","author":[{"given":"Kaley","family":"Whitmont","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Sutton Arthritis Research Laboratory, Institute of Bone and Joint, Kolling Institute of Medical Research University of Sydney at Royal North Shore Hospital  St Leonards NSW Australia"},{"name":"Department of Dermatology Royal North Shore Hospital  St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly J","family":"McKelvey","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Sutton Arthritis Research Laboratory, Institute of Bone and Joint, Kolling Institute of Medical Research University of Sydney at Royal North Shore Hospital  St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Fulcher","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism Royal North Shore Hospital  St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Sutton Arthritis Research Laboratory, Institute of Bone and Joint, Kolling Institute of Medical Research University of Sydney at Royal North Shore Hospital  St Leonards NSW Australia"},{"name":"High Risk Foot Service Royal North Shore Hospital  St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyn","family":"March","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Institute of Bone and Joint Research, University of Sydney  St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilang","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Sutton Arthritis Research Laboratory, Institute of Bone and Joint, Kolling Institute of Medical Research University of Sydney at Royal North Shore Hospital  St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Dermatology Royal North Shore Hospital  St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Sutton Arthritis Research Laboratory, Institute of Bone and Joint, Kolling Institute of Medical Research University of Sydney at Royal North Shore Hospital  St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,7,15]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2009.00541.x"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006534-200003000-00031"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.12968\/jowc.2008.17.1.27917"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2008.04.023"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/08977190410001701005"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.18.1.64"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.6.1856"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.sap.0000198731.12407.0c"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-5214(95)70245-8"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.21.5.822"},{"key":"e_1_2_5_12_1","unstructured":"Ortho\u2010McNeil Pharmaceuticals Inc. 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