Elsevier

Phytomedicine

Volume 14, Issue 1, 10 January 2007, Pages 2-10
Phytomedicine

Efficacy of a comfrey root (Symphyti offic. radix) extract ointment in the treatment of patients with painful osteoarthritis of the knee: Results of a double-blind, randomised, bicenter, placebo-controlled trial

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Abstract

This randomised, double-blind, bicenter, placebo-controlled clinical trial investigated the effect of a daily application of 6 g Kytta-Salbe® f (3×2 g) over a 3 week period with patients suffering from painful osteoarthritis of the knee.

The two hundred and twenty patients examined consisted of 153 women and 67 men of an average age of 57.9 years. On average, the complaints relating to osteoarthritis of the knee had persisted for 6.5 years. Two hundred and twenty patients were included in the Full Analysis Set (FAS) and safety collective, 186 (84.5%) in the Valid Case Analysis Set (VCAS) collective.

In the course of the trial, the visual analog scale (VAS) total score (primary target value) in the verum group dropped by 51.6 mm (54.7%) and in the placebo group by 10.1 mm (10.7%). The average difference between the groups of 41.5 mm (95% confidence interval=34.8 to 48.2 mm) or 44.0% is significant (p<0.001). The significance is confirmed through the evaluation of the diary, the VCAS evaluation and the separate assessment of the two centres. This also applies to the separate assessment of the VAS total score following pain at rest and on movement.

The WOMAC (Western Ontario and McMaster Universities) total score (secondary target value) also improved similar to the VAS total score. At the end of the trial, a reduction by 60.4 mm (58.0%) was recorded for the verum group and a reduction of 14.7 mm (14.1%) for the placebo group. The average group difference of 45.7 mm (95% confidence interval=37.1 to 54.3 mm) or 43.9% is significant (p<0.001).

The difference between the treatment groups increased systematically and significantly, in parallel with the duration of the treatment. Thus, the superiority of the treatment with Kytta-Salbe® f over that with the placebo is proven, even by means of the multi-factorial multivariate analysis for repetitive measurements.

In respect of the explorative secondary target values SF-36 (quality of life), angle measurement (mobility of the knee), CGI (clinical global impression) and global assessment of efficacy by the physician and the patient, a significant superiority (p<0.001 each) of the verum group over the placebo group was also proven.

The results suggest that the comfrey root extract ointment is well suited for the treatment of osteoarthritis of the knee. Pain is reduced, mobility of the knee improved and quality of life increased.

Introduction

Rheumatic disorders have different causes (inflammatory, infectious, degenerative, metabolic), are located at different parts of the body (joints, tendons, muscles, spine) and have different symptoms. Among them are several chronic tissue diseases and painful disorders of the locomotor system, including osteoarthritis of the joints.

Osteoarthritis characterises a primarily non-inflammatory, degenerative change of the structure of the cartilage and bones of one or more joints, involving an increasing deformation of the joint. On principle, all joints can be affected; frequently knee and hip joints, hands and the spine are affected. The frequency of osteoarthritis rises with age, approximately 80% of people over 75 are affected (Cooper, 1998). Osteoarthritis of the knee is described by the Deutsche Gesellschaft für Rheumatologie (German Rheumatology Association) as a disease primarily of the joint cartilage which coincides clinically with pain (pain upon walking, pain on exercise), limited movement and walking impairment, and can result in instability, false position and concomitant synovialitis (active athrosis) (Deutsche Gesellschaft für Rheumatologie, 2000).

The multitude of diseases and complaints is faced by an equally large number of therapeutic drug-based and non-drug based treatment options (Walker-Bone et al., 2000, Hunter and Felson, 2006). Due, in particular, to the symptoms: pain, joint stiffness and restriction of movement, patients seek therapeutical advice. As a result, symptomatic improvement represents an important therapeutic objective. The reduction of pain, the preservation and the restoration of the joint's function and thus the restoration of quality of life are therefore important target parameters in clinical trial (Förster, 2005).

The phytopharmaceutical drugs used in Germany are made, for instance, from willow bark and comfrey root. Since antiquity, the medicinal plant comfrey has been used both internally and externally in different forms of administration, for the treatment of a variety of diseases, e.g. bone fractures, wounds and ulcers (Englert et al., 2005).

In recent times, several clinical trials have proven the efficacy of comfrey in the treatment of distorsions, strains and sprains and other muscle and joint complaints (Koll et al., 2004; Predel et al., 2005; Kucera et al., 2005, Staiger, 2005).

In recent observation studies a reduction of pain of approx. 50% in respect of joint pain and a virtually complete decline of morning stiffness was observed after approximately two weeks of treatment with preparations containing comfrey root extract (Klingenburg, 2004; Tschaikin, 2004).

The efficacy of comfrey is essentially due to its anti-inflammatory, analgesic, granulation promoting and antiexsudative properties (Kommission E, 1990, Schmidtke-Schrezenmeier et al., 1992). Allantoin, rosmarinic acid and other hydroxycinamon acid derivatives as well as muco-polysaccharides are likely to be of critical importance for the pharmacodynamics of the root drug (Andres et al., 1989; Gracza et al., 1985).

Section snippets

Patients and methods

The clinical trial was performed in accordance with the ICH-GCP guidelines and the Declaration of Helsinki. The patients were informed prior to commencement of the trial and provided written confirmation of their participation in the trial.

This double-blind, randomised, bicenter, placebo-controlled trial involved a total of 220 patients with painful osteoarthritis of the knee. Both ambulatory centres were located in Berlin, Germany. Principal investigator was Barbara Grube, Kurfürstendamm

General information

A total of 220 patients (153 female, 67 male) were randomised and received trial medication after providing written agreement of their participation in the trial (FAS and Safety population). The patients were of an average age of 57.9 years. The complaints relating to osteoarthritis of the knee had on an average persisted for 6.5 years.

There was no significant group difference with regard to distribution of sex, age, height, and body weight. 44 of the 220 patients (20%) suffered from

Discussion

Osteoarthritis of the knee is among the most frequent degenerative joint diseases within the rheumatic disorders. This is due primarily to the complexity of the knee's structure, the high level of stress it is under from body weight but also to the increasing age of the population of industrialised countries. The primary, conservative treatment of osteoarthritis of the knee is symptomatic, as monotherapy or in combination with physical, physiotherapeutical and drug-based measures.

The most

Conclusions

The fact that the verum medication is significantly superior to the placebo medication with regard to all target values proves the therapeutic efficacy of the comfrey root extract ointment in the treatment of painful osteoarthritis of the knee.

At the end of the trial, pain in the verum group had, on an average, reduced five times more than in the placebo group. The primary target value (VAS total score) improved by 54.7% in the verum group, but only by 10.7% in the placebo group.

With regard to

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