Effects of ozone for treating chronically refractory wounds and ulcers A protocol for systematic review and meta-analysis of randomized clinical trials

Background: The prevalence of chronically refractory wounds and ulcers is growing rapidly. However, the treatment options are not completely effective. Ozone has been demonstrated as being useful in promoting wound healing as well as adverse events in individual studies. Consequently, it is necessary to conduct a meta-analysis of high-quality trials to find out whether ozone therapy is effective and safe in these chronic wounds. Methods: We will search the Cochrane Library, PubMed, the Web of Science, Embase, CBM, and the Chinese Clinical Registry website without restriction on language, date, or study setting. Randomized controlled trials of ozone therapy for chronical wounds or ulcers will be retrieved in diverse databases from inception to May 2020. The primary outcome of the meta-analysis is the proportion of participants with completely healed wounds; time to achieve complete ulcer healing; change in wound size. The secondary outcomes include the incidence of adverse events, amputation, quality of life, length of hospital stay, and cost. Two reviewers will adopt the Cochrane Collaboration's risk of bias tool to assess the randomized controlled trials and all relevant data will be analyzed by utilizing the Review Manager software V5.3.0. Results: This study will offer a high-quality synthesis of the effectiveness and safety of ozone for treating chronically refractory wounds and ulcers. Conclusion: This systematic review and meta-analysis will find out the available evidence to assess whether ozone therapy is beneficial to wound healing and side effects, producing evidence reference for clinical practice on the treatment of wound care.