title: Treatment of chronic diabetic lower leg ulcers with activated protein C: a randomised placebo-controlled, double-blind pilot clinical trial.
abstract: Lower leg ulcers are a serious and long-term complication in patients with diabetes and pose a major health concern because of the increasing number of patients diagnosed with diabetes each year. This study sought to evaluate the clinical benefit of topical activated protein C (APC) on chronic lower leg ulcers in patients with diabetes. Twelve patients were randomly assigned to receive either APC (N = 6) or physiological saline (placebo; N = 6) in a randomised, placebo-controlled, double-blind pilot clinical trial. Treatment was administered topically, twice weekly for 6 weeks with final follow-up at 20 weeks. Wound area was significantly reduced to 34·8 ± 16·4% of week 0 levels at 20 weeks in APC-treated wounds (p = 0·01). At 20 weeks, three APC-treated wounds had completely healed, compared to one saline-treated wound. Full-thickness wound edge skin biopsies showed reduced inflammatory cell infiltration and increased vascular proliferation following APC treatment. Patient stress scores were also significantly reduced following APC treatment (p < 0·05), demonstrating improved patient quality of life as assessed by the Cardiff Wound Impact Questionnaire. This pilot trial suggests that APC is a safe topical agent for healing chronic lower leg ulcers in patients with diabetes and provides supporting evidence for a larger clinical trial.
authors.affiliation: 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.|Department of Dermatology, Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: Kaley
authors.initials: K
authors.lastname: Whitmont
authors.affiliation: 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.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: McKelvey
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: Gregory
authors.initials: G
authors.lastname: Fulcher
authors.affiliation: 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.|High Risk Foot Service, Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Reid
authors.affiliation: Department of Rheumatology, Institute of Bone and Joint Research, University of Sydney, St Leonards, NSW, Australia.
authors.forename: Lyn
authors.initials: L
authors.lastname: March
authors.affiliation: 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.
authors.forename: Meilang
authors.initials: M
authors.lastname: Xue
authors.affiliation: Department of Dermatology, Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Cooper
authors.affiliation: 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.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Jackson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease / Q000188:drug therapy; D017719:Diabetic Foot / Q000175:diagnosis* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007871:Leg Ulcer / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011486:Protein C / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D011486:Protein C
keywords: Activated protein C; Diabetes; Ulcer; Wound healing