Abstract

Objectives: A previously published study comparing the efficacy of comfrey extract to a commercial diclofenac (CAS 78213-16-8) preparation in the treatment of unilateral ankle sprains is critically re-evaluated. The study was designed to show non-inferiority of the comfrey extract. The data were re-evaluated for superiority according to CPMP guidelines. The study was an observer-blind, randomised, multi-centre clinical trial with two independent treatment groups "comfrey extract" and "diclofenac gel" (parallel group design) and included a total of 164 patients (82 in the comfrey group and 82 in the diclofenac group, intention-to-treat (ITT) analysis). Key variables were the area under the curve (AUC) from Visits 1 to 2 of the difference of the tenderness values contra-lateral minus injured side (primary variable), pain assessment (Visual Analogue Scale, VAS) at rest and on movement by patient, swelling (figure-of-eight method) and ankle movement (neutral zero method). On average (mean difference comfrey extract minus diclofenac), the AUC was +61.1 h x N/cm2 greater for patients treated with comfrey extract compared to diclofenac treated patients (95% confidence interval: 19.08; 103.09 h x N/cm2). The difference between the two treatment groups was statistically significant (analysis of variance with factors "study drug", "centre", and "drug x centre interaction"). Safety was excellent in both treatment groups. The re-evaluation of the data showed superiority of the plant based ointment over the diclofenac gel in the treatment of distortions. It is encouraging and impressive to realize that a natural product seems to be an effective and safe alternative to the standard topical treatment with diclofenac.