Randomized, Controlled Study of Innovative Spray Formulation Containing Ozonated Oil and !-Bisabolol in the Topical Treatment of Chronic Venous Leg Ulcers Laura Gheuca ˘ Solova ˘stru, MD, PhD; Alina Stı ˆncanu, MD; Alessia De Ascentii, PhD; Guido Cappare ´, MD; Paolo Mattana; and Dan Va ˆ ¢a ˘, MD, PhD ABSTRACT OBJECTIVE: Ozone therapy has a large clinical application in many therapeutic areas because of its well-known antimicrobial, immunological, and oxygenating properties. Recently, interest has grown regarding the application of ozonated oil for vascular leg ulcer treatment. The efficacy of an innovative spray formulation of ozonated oil and !-bisabolol combination in the topical treatment of chronic venous leg ulcers was evaluated compared with standard epithelialization cream. DESIGN: A randomized controlled trial was conducted. SETTING: A total of 29 patients older than 18 years with chronic venous leg ulcers for less than 2 years’ duration were assessed. PATIENTS: Patients were randomized to receive daily application of both ozonated oil and !-bisabolol or the control cream (vitamin A, vitamin E, talc, and zinc oxide) for 30 days. MAIN OUTCOME MEASURES: Patients were evaluated on 4 different visits: at days 0, 7, 14, and 30. At each visit, the wound surfaces were measured. Wound area ratio and the speed of ulcer healing were calculated. MAIN RESULTS: At the end of treatment, the proportion of patients with complete ulcer healing was higher with ozonated oil and !-bisabolol formulation (25% vs 0%). Furthermore, the changes in ulcer surface area were significant for ozonated oil and !-bisabolol formulation only (P G .05), in particular, observing a significant and progressive reduction of the wound surface by 34%, 59%, and 73%, after 7, 14, and 30 days of treatment, respectively. CONCLUSION: The innovative spray formulation of ozonated oil and !-bisabolol combination shows promise as an important new therapeutic option in the adjuvant treatment of venous ulcers. KEYWORDS: !-bisabolol, ozonated oil, topical wound treatment, venous leg ulcer ADV SKIN WOUND CARE 2015;28:406Y9 INTRODUCTION Chronic leg wounds result in diminished quality of life, frequent hospitalizations and healthcare provider visits, and increased mor- bidity and mortality. 1 Many leg ulcers are secondary to venous disease, and epidemiological data presume that approximately 10% of patients with chronic venous disease develop an ulcer. 2 In addition, approximately 55% to 70% of all patients with vascular lower- extremity ulcers have a venous etiology. 3Y5 These data represent between 0.2% and 1% of the total population and between 1% and 3% of the older adult population in the United States and Europe. 1 Despite various treatment approaches, including the standard compression therapy, the median duration of an ulcer has been longer for venous ulcers versus nonvenous ulcers. 6 The healing time of venous leg ulcers has generally ranged from 40% to 80% within 3 to 6 months. 3,7,8 Furthermore, venous ulcers are often recurrent, and open ulcers can persist from weeks to many years. 9 For these reasons, it is important to explore advancements in the treatment and management of chronic venous ulcers. Wounds generally follow a well-defined wound healing pro- cess that involves 4 main stages: coagulation, inflammation, cell proliferation and repair of the matrix epithelialization, and remod- eling of the scar tissue. 10 Many studies have demonstrated that endogenous growth fac- tors, such as fibroblast growth factors, 11 platelet-derived growth factors, 12 transforming growth factor A, 13 and vascular endothelial growth factors, 14 are the important regulatory polypeptides in the healing process. They are released from macrophages, fibroblasts, and keratinocytes at the site of injury and participate in the reg- ulation of re-epithelialization, granulation tissue formation, collagen synthesis, and neovascularization. From a practical perspective, wound healing depends on many factors, including wound bed preparation, and the management of the critical factors summarized in the mnemonic ‘‘TIME’’ framework, ADVANCES IN SKIN & WOUND CARE & VOL. 28 NO. 9 406 WWW.WOUNDCAREJOURNAL.COM ORIGINAL INVESTIGATION Laura Gheuca ˘ Solova ˘ stru, MD, PhD, is Associate Professor, Dermatology Department, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania. Alina Stı ˆncanu, MD, is a Dermatologist, Dermatology, Saint Spiridon Emergency Hospital, Iasi, Romania. Alessia De Ascentii, PhD, is a Scientist, Cosmoproject srl in Casale di Mezzani, and Neovalis srl, Parma, Italy. Guido Cappare ´ , MD, is a General Practitioner, Lauderma Clinic, Iasi, Romania. Paolo Mattana is a Biologist and Scientific Advisor, Medical Service, Alfa Wassermann, Bologna, Italy. Dan Va ˆ ¢a ˘, MD, PhD, is Assistant Professor, Dermatology Department, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania. Dr Solova ˘stru has disclosed that she was a consultant for Comsmoproject and was a member of the speakers’ bureau for Pfizer and Berlin Chemie. Paolo Mattana has disclosed that his employer, Alfa Wassermann, is the pharmaceutical company that markets Azexin (the topical product base of ozonated oil and object of the study). The remaining coauthors have disclosed that they have no financial relationships related to this article. The authors have disclosed that the article discusses the investigational use of ozonated sunflower oil and !-bisabolol spray formulation in the topical treatment of chronic venous leg ulcers. Submitted January 21, 2014; accepted in revised form April 15, 2014. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.