Abstract

Objective: To compare the effectiveness and safety of the triple combination Phlogenzym (rutoside, bromelain, and trypsin) with double combinations, the single substances, and placebo.

Design: Multinational, multicentre, double blind, randomised, parallel group design with eight groups structured according to a factorial design.

Setting: Orthopaedic surgery and emergency departments in 27 European hospitals.

Participants: A total of 721 patients aged 16–53 years presenting with acute unilateral sprain of the lateral ankle joint.

Primary efficacy criteria: (a) Pain on walking one or two steps, as defined by the patient on a visual analogue scale. (b) The range of motion, as measured by the investigator and expressed as a sum of flexion and extension. (c) The volume of the injured ankle measured with a volometer.

Results: At the primary end point at seven days, the greatest reduction in pain was in the bromelain/trypsin group (73.7%). The Phlogenzym group showed a median reduction of 60.3%, and the placebo group showed a median reduction of 73.3%. The largest increase in range of motion (median) was in the placebo group (60% change from baseline). The Phlogenzym group showed a median increase of 42.9%. The biggest decrease in swelling was in the trypsin group (3.9% change from baseline). The Phlogenzym group showed a −2.30% change from baseline and the placebo group a −2.90% change. In the subgroup analysis of patients who did not use a Caligamed brace, Phlogenzym was superior to placebo for the summarising directional test of the primary efficacy criteria (MW  =  0.621; LB-CI 0.496; p  =  0.029; one sided Wei-Lachin procedure). The vast majority of doctors and patients rated the tolerability of all treatments tested as very good or at least good.

Conclusions: Phlogenzym was not found to be superior to the three two-drug combinations, the three single substances, or placebo for treatment of patients with acute unilateral sprain of the lateral ankle joint. The small subgroup of patients treated without the support of a Caligamed brace showed evidence of superiority of Phlogenzym over placebo. Further research is warranted to study this effect of Phlogenzym in patients treated without ankle support.