Tr14 gel compared to diclofenac gel after acute unilateral ankle sprain: an Individual Patient Data (IPD) meta-analysis of two multi-center trials

Abstract Background Traumeel (Tr14) and diclofenac gels are commonly prescribed topical treatments for Grade I-II acute lateral ankle sprain (LAS). A meta-analysis of two multi-center trials was performed to compare their clinical efficacy and supplement the evidence in support of topical treatments. Methods Data from two Phase III prospective, randomised, double-blind, reference-controlled clinical trials, TAASS (2013) and TRAUMED (2024) were examined. An Individual Patient Data (IPD) meta-analysis was performed on those with an initial pain VAS (Visual Analogue Scale) score ≥ 50 mm, using the statistical analysis plan from the latter to ensure methodological consistency. Results A total of 628 patients underwent meta-analysis (mean baseline pain VAS = 72.3, mean age = 32.5). The primary endpoint of the IPD meta-analysis, Area Under the Curve (AUC) of pain VAS scores, indicated beneficial effects of Tr14 gel compared with diclofenac gel, statistically significant on Days 4, 7, and 14 (Day 4 mean difference MDAUC-META = -6.9 [95%CI -13.7 to -0.1], PAUC-META = 0.05; Day 7 MDAUC-META = -26.3 [95%CI -40.4 to -12.2], PAUC-META = 0.0003; Day 14 MDAUC-META = -63.6 [95%CI -92.3 to -34.8]), PAUC-META < 0.0001). A robust Wilcoxon-Mann-Whitney (WMW) analysis revealed percent changes from baseline in pain and function that were significantly superior for Tr14 gel in the pre-planned method of synthesis, compared to diclofenac gel, on all days (all PMETA < 0.05). Finally, translational effect sizes indicated less than “small” superiority on Day 4 (SMD 0.15, OR 0.78, NNT 23), and “small-medium-sized” superiority on Days 7 and 14 (Day 7: SMD 0.31, OR 0.59, NNT 12; Day 14: SMD 0.37, OR 0.53, NNT 10) for pain measured by VAS, as compared to diclofenac gel. Conclusion The IPD meta-analysis of the TAASS and TRAUMED trials confirms the efficacy of Tr14 gel. In-depth analysis reveals it is a statistically favourable treatment with respect to pain, and function, compared to the gold-standard diclofenac gel. Taking this together, Tr14 gel represents a statistically favourable treatment option for Grade I–II ankle sprain within the context of the analysed endpoints.