Efficacy and safety of topical diclofenac/menthol gel for ankle sprain: A randomized, double-blind, placebo- and active-controlled trial

Abstract

Purpose This study was performed to evaluate topical 1% diclofenac/3% menthol gel in treating ankle sprain. Design In this randomized, double-blind, placebo-controlled trial, adolescents and adults with acute ankle sprain (N = 385) applied 4 g of gel containing 1% diclofenac/3% menthol (n = 117), 1% diclofenac (n = 112), 3% menthol (n = 77), or placebo (n = 75) four times daily. The primary outcome was the area under the curve of pain intensity (PI) on movement [0 (no pain) to 10 (extreme pain)] from 24 to 72 hours post-application (AUC_{1-3 days}). Secondary outcomes included pain relief (PR); PI; time to onset of PR, meaningful PR, cooling, and complete recovery; PI difference; sum of PI difference; total PR; reduction in ankle swelling; and the patient's global assessment of response to treatment. Results There were no statistically significant differences in AUC_1-3 between 1% diclofenac/3% menthol and placebo, diclofenac, or menthol gels and no meaningful advantages of 1% diclofenac/3% menthol for any secondary outcome. There was a higher incidence of skin and application-site events with 1% diclofenac/3% menthol than with placebo or 1% diclofenac. Conclusion No significant improvement was observed with topical 1% diclofenac/3% menthol gel compared with placebo, 1% diclofenac, or 3% menthol gel in treating pain from ankle sprain. ClinicalTrials.Gov Identifier: NCT02100670.

Keywords: Ankle sprain; diclofenac; menthol; pain; topical administration.

Figure 1.

Patient flow. ^aAll patients who received at least one dose of medication also provided at least one post-baseline assessment; therefore, the safety and intent-to-treat populations were identical.

Figure 2.

Adjusted mean pain relief ratings with 1% diclofenac/3% menthol gel compared with 1% diclofenac gel, 3% menthol gel, and placebo in the intent-to-treat population. Pain relief was assessed using a 5-point scale: 0 = no pain relief, 1 = a little or perceptible pain relief, 2 = meaningful pain relief, 3 = a lot of pain relief, and 4 = complete pain relief. The adjusted mean pain relief rating score is the least squares mean from the mixed model analysis of covariance, with treatment and site as fixed effects and pain intensity at baseline as a covariate.