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
References (40)
- et al.
Efficacy and tolerance of a comfrey root extract (Extr. Rad. Symphyti) in the treatment of ankle distorsions: results of a multicenter, randomized, placebo-controlled, double-blind study
Phytomedicine
(2004) - et al.
Anti-inflammatory effect of diclofenac-sodium ointment (cream) in topical application
Jpn. J. Pharmacol.
(1983) - et al.
Relating antiphlogistic efficacy of dermatics containing extracts of Symphytum-officinale to chemical profiles
Planta Med.
(1989) - et al.
Local tolerability and pharmacokinetic profile of a new transdermal delivery system, diclofenac hydroxyethylpyrrolidine plaster
Drugs Exp. Clin. Res.
(1993) - et al.
Comparison of the analgesic and anti-inflammatory effects of diclofenac potassium versus piroxicam versus placebo in ankle sprain patients
J. Int. Med. Res.
(1990) - et al.
Comparison of the efficacy and tolerability of diclofenac gel (Voltarol Emulgel) and felbinac gel (Traxam) in the treatment of soft tissue injuries
Br. J. Clin. Pract.
(1990) Symphytum officinale (comfrey) ointment relieves pain and swelling after ankle distortion
Focus Altern. Complement. Ther.
(2005)- et al.
Einfluß einer topischen Behandlung auf den Krankheitsverlauf bei Sprunggelenks-Distorsionen
Arzneim. Forsch./Drug Res.
(1987) - et al.
A double-blind study of the efficacy of nimesulide in the treatment of ankle sprain in comparison with placebo
Drugs
(1993) - EMEA, 2000. CPMP/EWP/482/99, Points to consider on switching between superiority and non-inferiority, 27...
Symphytum officinale L. Der “Beinwell” in der europäischen Pharmazie- und Medizingeschichte
Z. Phytother.
Wirkung einer Symphytum-Salbe bei Sportverletzungen des Kniegelenks
Dtsch. Z. Sportmed.
Measurement of pain
Lancet
Measurement of pain
J. Rheumatol.
Symphytum officinale – Beinwell
Ztsch. Phytother.
Therapeutische Eigenschaften und Verträglichkeit topischer Beinwellzubereitungen. Ergebnisse einer Beobachtungsstudie an Patienten
Fortschr. Med.
Cited by (55)
Penetration of lycopsamine from a comfrey ointment through human epidermis
2017, Regulatory Toxicology and PharmacologyThe external use of comfrey: A practitioner survey
2014, Complementary Therapies in Clinical PracticeCitation Excerpt :Some of the respondents' opinions regarding effectiveness are supported by the literature. A recent critical scoping review of comfrey [16] found a modest evidence base for the use of comfrey in reducing pain in ankle distortion [37–39], acute back pain [40,41] and osteoarthritis [42–45] and for the treatment of abrasion wounds in adults and children [46,47]. However, this does contrast herbalists' lower usage and opinions of effectiveness for back pain and arthritis.
A critical scoping review of external uses of comfrey (Symphytum spp.)
2013, Complementary Therapies in MedicineCitation Excerpt :Twenty of these provided tolerability outcome data.41–50,52,54,55,59–62,64–66 Nineteen reported the incidence of AEs41–50,52,54,55,59–62,64,66 and five provided information about the AE data collection method.43–46,62 One study included patient- and physician-rated local tolerance but no AE details.65
Topical analgesics in the management of acute and chronic pain
2013, Mayo Clinic ProceedingsCitation Excerpt :Evidence for efficacy and tolerability of a specific topical analgesic was reviewed only if 2 or more published clinical trials were available for that drug, irrespective of indication; in other words, if a particular disease state was the focus of only one published clinical trial but the topical analgesic that was studied in that clinical trial was studied in at least one other clinical trial, then that clinical trial was included in the review. The literature search identified a total of 92 articles, of which 65 were eligible for inclusion (Figure).29-92 A total of 27 articles were excluded: 7 articles93-99 described studies in which the analgesic was not administered topically; 6 articles100-105 described clinical trials of nonpharmacologic treatments (ie, ice, heat, or practitioner advice); 5 articles106-110 focused on analgesics that were studied in only 1 clinical trial; 3 articles111-113 dealt with ophthalmic indications rather than acute or chronic pain; 3 articles114-116 were reviews; 1 article117 described an experimental study in which capsaicin was used as a stimulus rather than as a therapy; 1 article118 described a mathematical modeling study; and 1 article119 dealt with a pharmacokinetic study with no pain assessment.