Efficacy of a Comfrey root extract ointment in comparison to a Diclo-fenac gel in the treatment of ankle distortions: Results of an observer-blind, randomized, multicenter study
Introduction
Both topical drugs tested in this clinical trial are well known as state-of-the-art pharmacological treatments of minor blunt injuries. The therapeutic properties of comfrey are based on its anti-inflammatory and analgesic effects as well as its activity in stimulating granulation and tissue regeneration (Andres et al., 1989; Koehler and Franz, 1987). Comfrey (Symphytum officinale L.) is a medicinal plant with a long heritage and tradition in the treatment of painful muscular and joint complaints (Englert et al., 2005; Kothmann, 2003; Prinzing, 1960), proven in numerous studies (Hess, 1991; Koll and Klingenburg, 2002; Kucera et al., 2000; Mayer, 1991, Mayer, 1992, Mayer, 1993; Pabst and Ottersbach, 2004; Petersen et al., 1993; Schmidtke-Schrezenmeier et al., 1992; Tschaikin, 2004). For the pharmacological effect and clinical efficacy of comfrey preparation at topical application three major constituents of comfrey might be responsible: the purin derivative allantoine, rosmarinic acid and the mucilages (polysaccharides) (Wagner and Wiesenauer, 2003). Recent clinical trials again prove the efficacy in bruises, strains, contusion, and sprains.
In 1999, a preparation of Comfrey root extract (1:2, ethanol 60% V/V, 35%, Kytta Salbe® f) was compared to placebo in a multicenter, randomized, double-blind, parallel group study in 142 patients suffering from a unilateral ankle sprain. Treatment was started at the latest 6 h after occurrence of the injury. The duration of treatment was 8 days and assessments were made on days 0, 4 and 7. The affected ankle joint was locally treated with about 2 g of ointment four times a day. The primary variable was tenderness of the ankle joint, measured by tonometry (pressure difference between the injured and healthy foot). During the course of treatment, pain regressed significantly more in the group with Comfrey extract than in the placebo group. At the final measurement, the reduction compared to initial tenderness was 2.44 kp/cm2 in the active treatment group whilst it was only 0.95 kp/cm2 under placebo. Compared to placebo, verum was clearly superior regarding the reduction of pain (tonometric measurement, ) and ankle edema (figure-of-eight method, ). Significant differences between active treatment and placebo could also be revealed for ankle mobility (neutral-zero method), and global efficacy (Koll et al., 2004).
In a controlled, double-blind, randomized multicenter study, the efficacy and safety of a topical Comfrey extract product (10% active ingredient of a 2.5:1 aqueous ethanolic Comfrey extract (Symphytum×uplandicum NYMAN), corresponding to 25 g of fresh herb per 100 g of cream; ) was tested against a 1% product (corresponding to 2.5 g of fresh comfrey herb in 100 g of cream; ) in 203 patients with acute ankle sprains. With the high concentration, decrease of the scores for pain during active motion, pain at rest and functional impairment was highly significant and clinically relevant on days 3–4 as well as on day 7 (). Amelioration of swellings as compared to reference was also significant on days 3–4 (). Efficacy was judged good to excellent in 85.6% of cases with verum and in 65.7% of cases with reference on days 3–4 (Kucera et al., 2004).
Diclofenac acts as a potent cyclooxigenase inhibitor. Its pharmacological properties are well documented and generally known (Hardman and Limbird, 1996; Sweetman, 2004). Pharmacokinetic trials have shown that diclofenamic acid, when applied topically, penetrates the skin barrier to reach joints, muscles and synovial fluid, in sufficiently high concentration to exert local therapeutic activity (Assandri et al., 1993; Radermacher et al., 1991; Riess et al., 1986). Several clinical trials on diclofenac have been published and prove the efficacy not only on blunt injuries but further muscle and joint complaints like activated osteoarthritis of the finger joints (Bahamonde and Saavedra, 1990; Bouchier-Hayes et al., 1990; Kyuki et al., 1983; Predel et al., 2004; Zacher et al., 2001).
Section snippets
Methods and substances
This clinical study (CODEC_2004) was planned and carried out as a multicenter, controlled trial (two parallel groups) with patients suffering from unilateral ankle sprains. The two groups were treated either with commercially available Kytta-Salbe® f or Voltaren® Schmerzgel (Voltaren, 1999, Kytta, 2001).
A double-blind design was not possible due to the differences between the two products (cream vs. gel, color, odour). Therefore, the study was carried out as an “investigator-blind” trial: at no
General data
A total of 164 male and female outpatients were randomized and took the study medications after having given written informed consent. All randomized patients were assessed for efficacy in the intention-to-treat and per protocol population. There were 82 patients (50.0%), aged on average 29.6 years, randomized to Comfrey extract and 82 patients (50.0%), aged on average 28.4 years, randomized to Diclofenac gel. All of the patients were Caucasians. A history of allergy was reported in 48 cases
Discussion
The two topical drugs tested in this clinical trial are well known as state-of-the-art pharmacological treatments of minor blunt injuries (De Lange de Klerk, 2005). They represent, however, two fundamentally different major pharmacological therapy approaches: the “chemical-synthetical” and the “phytotherapeutical” approach, the one being a pure synthetic product and the other being a plant extract. A direct comparison of these two therapies has not been described before and is of quite some
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