Diclofenac Sodium Topical Gel (DSG) 1% Reduces Swelling and Tenderness and Improves Ankle Joint Function in Subjects with Acute Ankle Sprain: A Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVES: Ankle sprains are among the most common sports-related injuries and are often self-treated. Over-the-counter treatment options known to reduce pain and inflammation, such as oral non-steroidal anti-inflammatory drugs (NSAIDs), may be associated with systemic side effects (e.g. gastrointestinal), while topically applied rubefacients are frequently ineffective, despite their popularity. DSG 1%, which has been clinically proven to be effective and well-tolerated for the treatment of osteoarthritis, could be a new option for the treatment of acute injuries, such as ankle sprains. This study evaluated the efficacy and safety of DSG 1% applied q.i.d in subjects with acute ankle sprain. METHODS: In a double-blind, multicenter study, 205 subjects with acute sprain of the lateral ankle (Grade l-ll) were randomized in a 1:1 ratio to DSG 1% (n=102) or placebo (n=103) applied q.i.d for 7 days. The primary efficacy outcome was pain-on-movement (POM) at 72 hours, assessed on a 100 mm visual analog scale (VAS). Secondary efficacy outcomes included ankle swelling assessed by circumference measurement compared with the non-affected ankle, tenderness measured by pressure algometry compared with the non-affected ankle, and ankle joint function assessed by the Karlsson scoring scale. Efficacy assessments were conducted at clinic visits at 12, 24, and 72 hours and 7 days after treatment initiation. All adverse events were recorded and blood samples were collected for laboratory safety analysis. RESULTS: DSG 1% treatment resulted in a significant decrease of POM mean scores when compared with placebo (57 mm vs. 21 mm respectively; p<0.0001). DSG 1% treatment also resulted in significantly greater reductions in ankle swelling than placebo. The difference in circumference between the injured and non-affected ankles for subjects treated with DSG 1% vs. placebo was 1.9 cm vs. 2.4 cm at 12 hours, 1.4 cm vs. 2.0 cm at 24 hours, 0.8 cm vs. 1.5 cm at 72 hours, and 0.2 cm vs. 0.8 cm at 7 days (p<0.0001 at all time points). In subjects treated with DSG 1%, the mean difference in tenderness between the injured and non-affected ankles decreased more rapidly than in subjects in the placebo group at 12 hours (-24.7 N/cm(2 )vs. -28.5 N/cm(2)), 24 hours (-17.8 N/cm(2 )vs. -25.3 N/cm(2)), 72 hours (-9.7 N/cm(2 )vs. -19.8 N/cm(2)), and 7 days (-2.6 N/cm(2 )vs. -12.1 N/cm(2)) (p<0.0001 at all time points). In subjects treated with DSG 1%, the mean total ankle joint function score was 24.5 at baseline vs. 25.3 for the placebo group. At 72 hours and Day 7, mean ankle joint function scores were 56.3 and 79.7, respectively, for the DSG 1% group vs. 35.6 and 47.0, respectively, for the placebo group. The differences between treatment groups were significant at all time points (p<0.0001). The safety profile of DSG 1% was similar to that of placebo. CONCLUSION: DSG 1% applied 4 times daily was significantly superior to placebo in reducing pain, swelling and tenderness and improving ankle joint function in subjects with acute ankle sprain. Overall, DSG 1% was well tolerated both systemically and locally.