Efficacy and Safety of the Phytochemical Product Linfadren in the Management of Patients With Persistent Ankle Edema Following Trauma or Surgery: A Randomized Controlled Trial

Abstract

Background: Persistent posttraumatic/postsurgery ankle edema (PPAE) is edema that persists from 2 weeks to 3 months after injury or surgery. PPAE has negative effects on the healing process and quality of life. This study aimed to evaluate the efficacy of a phytochemical product containing diosmin, coumarin, and arbutin (Linfadren) in addition to the conventional treatment, in patients with PPAE. Methods: Between October 2018 and February 2020, 60 outpatients with PPAE (42 with ankle fractures and 18 with ankle sprains) were enrolled and randomized (1:1 ratio) to receive either 6-week conventional treatment plus Linfadren (study group) or conventional treatment alone (control group). Primary outcome was ankle edema as measured by the “figure-of-8-20” method. Secondary outcomes were ankle function measured by the Lower Extremity Functional Scale (LEFS), and patient’s overall perceived treatment efficacy. Tolerability of Linfadren was also evaluated. Assessments were performed at baseline, at end of treatment (6 weeks after baseline), and 3 months after the end of treatment (follow-up). A subgroup analysis was also conducted for the injury type (fracture/sprain) to identify if this factor affected the results of the primary outcome measure. Results: At the end of treatment, the study group had a significantly greater improvement in ankle edema, improved ankle function, and more patients who considered this treatment effective compared with the control group. The measured difference in circumference by the figure-of-8-20 method averaged 4% at 6 weeks and 5% at 3 months. No difference between groups was seen in rescue medication. No adverse events were recorded. Subgroup analysis revealed no significant influence of the injury type on the primary outcome measure. Conclusion: Linfadren in addition to conventional treatment was more effective than conventional treatment alone in patients with PPAE. Level of Evidence: Level I, randomized controlled trial.