Arzneimittelforschung 2007; 57(11): 712-716
DOI: 10.1055/s-0031-1296672
Analgesics · Anti-inflammatories · Antiphlogistics · Antirheumatic Drugs
Editio Cantor Verlag Aulendorf (Germany)

Comfrey Extract Ointment in Comparison to Diclofenac Gel in the Treatment of Acute Unilateral Ankle Sprains (Distortions)

Roberto D’Anchise
1   Istituto Ortopedico Galeazzi, Milano, Italy
Michael Bulitta
2   Clinical Research Management Biometrics GmbH (CRMB), Rheinbach, Germany
Bruno Giannetti
3   Clinical Research Management GmbH (CRM), Rheinbach, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
21 December 2011 (online)


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 “com-frey 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∙N/cm² greater for patients treated with comfrey extract compared to di-clofenac treated patients (95 % confidence interval: 19.08; 103.09 h∙N/cm²). The difference between the two treatment groups was statistically significant (analysis of variance with factors “study drug”, “centre”, and “drug∙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.