Arnica/Hydroxyethyl salicylate combination spray for ankle distortion: a four-arm randomised double-blind study

570 patients with acute ankle joint distortion were randomized to four treatment groups: a combination spray of arnica tincture and hydroxyethyl salicylate (HES; group A, n = 228), arnica (B, n = 57), HES (C, n = 228), and placebo (D, n = 57). The medication was applied 4-5 times daily for 10 days. Efficacy was assessed on day 3-4 by evaluating pain on motion on a visual analogue scale (VAS). Pain improvement in group A was significantly superior over groups B-D (t-test with unadjusted baseline values, P < 4 × 10(-7) and ANCOVA after adjustment, P < 5 × 10(-11)) and approximately corresponded to the cumulative effect of the single constituents (12.1, 7.5, and 18.7 mm VAS for A versus B, A versus C, and A versus D; 95% CI 8.0-16.2, 4.7-10.4, and 14.8-22.5 mm). The combination is justified by the additive effects of the single active constituents.