Research Review by Gary Maguire©

Date Posted:

September 2010

Study Title:

Efficacy and safety of comfrey root extract ointment in the treatment of acute upper or lower back pain: results of a double-blind, randomized, placebo controlled, multicentre trial

Authors:

Giannetti BM et al.

Author's Affiliations:

CRM Pharmaberatung GmbH, Rheinbach, Germany.

Publication Information:

British Journal of Sports Medicine 2010; 44: 637-641.

Background Information:

Back pain is a widespread condition impairing functional movement and quality of life in a large portion of the population. The general treatment approach consists of physiotherapy, chiropractic, therapeutic modalities and pharmacotherapy (both systemic and topical). Recently the use of topical anti-inflammatory substances, both pharmacologic (ex.diclofenac) and natural (ex. those containing capsaicin), has increased. Diclofenac has been studied frequently and has been shown to be efficacious in pain management, facilitating rehabilitation and achieving early recovery.

Phytotherapeutic preparations with comfrey have also been developed, and appear to be a safe and effective alternative to topical non-steroidal anti-inflammatory drugs (NSAID). This topical application has been considered a “state of the art” treatment option utilized in the management of pain in other muscle and joint complaints (i.e. blunt injuries or osteoarthritis).

Comfrey (symphytum officinale L) is a medicinal plant with a long history and tradition in the treatment of painful muscular and joint complaints (1). The efficacy of this root ointment (Kytta-Salbe f: Merck Selbstmedikation GmbH, Darmstadt, Germany; containing 60% V/V; less than 0.35ppm of pyrrolizidine alkaloids in the finished product) was evaluated in a randomized, double-blind, placebo controlled multicenter study involving 142 patient with unilateral ankle sprain. During the course of treatment pain regressed significantly more in the comfrey extract group than in the placebo group (p<0.001). Compared with the placebo, the superiority of verum treatment was significant with regard to a reduction in pressure pain, ankle edema, ankle mobility and global efficacy.

The same ointment was compared with a gel preparation containing 1% diclofenac in a randomized, single-blind multicenter study. The results showed that the comfrey ointment was equivalent or even better than diclofenac gel (2).

Other studies have also demonstrated positive results using comfrey ointment and it is therefore presumed that the ointment may also be efficacious in treating back pain due to the pathophysiologically close relationship of soft tissue injuries. That is what this double-blind, multicentre, randomized clinical trial aimed to evaluate.

Pertinent Results:

  • A total of 120 patients (average age ~37) were randomly assigned and received the study medications with equal distribution in each group (comfrey vs. placebo). The groups were well balanced in demographics and anamnestic data. No other analgesics were taken by patients in the clinical trial (except for one patient who took a paracetamol-containing drug for a cold).
  • The results revealed significant treatment differences between the comfrey extract and the placebo, with pain activity during active standardized movement decreasing 95.2% (comfrey extract) versus 37.8% in the placebo group. During the second treatment, pain intensity decreased approximately 33% (comfrey extract) versus 12% in the placebo group indicating an early onset of treatment effect.
  • Secondary outcomes also showed superiority of the comfrey including: area under the curve (AUC) of the reported back pain at rest, the AUC of the pressure algometry in the trigger point as well as the global assessment of efficacy by the patients the investigators showed significant superiority of the comfrey extract group (p value in all cases < 0.001).
  • Specifically, back pain at rest decreased by approximately 97.4% (comfrey group) versus 39.6% in the placebo group. Further, pressure algometry values increased by an average of 125% (comfrey group) versus 71.8% in the placebo group.
  • Overall the investigators documented an excellent assessment for 18 (30%), good for 30 (50%), fair for nine (15%), poor for two (3.3%) and none for one (1.7%) for patients receiving the comfrey extract treatment. The placebo group ratings were: excellent for one (1.7%), good for 10 (16.7%), fair for 24 (40%), poor for 22 (36.7%) and non for three (5%) of the patients.
  • Findings for global assessment of efficacy by the patients receiving comfrey extract were: excellent in 28 (46.7%), good in 19 (31.7%), fair in 10 (16.7%), poor in one (1.7%) and none in two (3.3%). The placebo patient group reported: excellent in one (1.7%), good in 10 (16.7%), fair in 18 (30%), poor in 28 (46.7%) and none in three (5%).
  • There were some safety concerns among both groups (four in the comfrey group vs. three in the placebo group) with all adverse events being of mild severity. One adverse effect in the comfrey group was related to the study drug. Overall the safety of both treatments under the given study conditions was rated as “excellent” which reflected the safety record of the comfrey root extract and the ointment base in research to date.

Clinical Application & Conclusions:

The authors of this study strongly suggest that all aspects of the clinical trial are clear-cut and consistent across all primary and secondary efficacy variables, and that comfrey root extract is remarkably potent and clinically relevant in reducing low back pain. Promising – yes – and their results seem to support this, but further research is required. Larger patient groups and comparisons with other treatment options for back pain would be good places to start. The good news is that this study appears to be easily reproducible and should encourage other investigators to substantiate the benefits of this therapeutic approach for alleviating back pain.

Study Methods:

The objective of this study was to demonstrate the superiority of comfrey root extract ointment versus a placebo ointment in patients with acute upper and lower low back pain. The study was structured as a double-blind, multicenter, randomized clinical trial with two independent treatment groups (parallel group design) performed over a 5 day period.
<>br/> A total of 120 patients (average age ~37) were randomly assigned and received the study medications with equal distribution in each group (comfrey vs. placebo). Inclusion criteria consisted of the presence of upper or lower back pain. Prior to randomization the patients were examined thoroughly obtaining all concomitant medication documentation and anamnestic data. Exclusion criteria were standard and appropriate for a trial on back pain.

The primary efficacy variable was the area under the curve (AUC) of the visual analogue scale (VAS) on active standardized movement during visits 1-4. AUC was determined using the cumulative trapezoidal rule (higher values of the AUC indicate greater pain). Secondary efficacy variables were back pain at rest using assessment of efficacy by the patient and investigator, consumption of analgesic medication and functional impairment measured using the Oswestry disability scale.

Patients were treated with verum or placebo ointment (4g/application - corresponding to a 12cm long cream layer). The cream was spread to the treated area and distributed by massage. Treatment commenced after enrollment into the trial and was administered 3x/day at intervals of approximately 8 h and continued for a total of 5 days.

The verum group was treated with Kytta-Salbe f. 100g contained 35g 99% PA reduced Rad Symphyti fluid extract (1:2, ethanol 60% [V/V]). The specification of the extract allows allantoin content of 0.2-0.5% (m/m). In comparison the placebo group was treated with the ointment base without active principles and with the same cream appearance.

Study Strengths / Weaknesses:

The study methods were appropriate, and substances used were clearly defined. Assessment tools were well described and appropriate, as were statistical analysis and procedure documentation. It should be noted that there were no competing interests in this study and a positive ethics committee approach was obtained from the Physicians” Chamber of Northrhein Westphalia, Germany.

EDITOR’S NOTE: For their primary outcome (AUC of the VAS) - the authors used a total score for the VAS of the upper back and lower back, with no attempt to define which region improved most, or contributed most to the original or subsequent scores. Readers should keep that in mind when interpreting the results of this study.

Additional References:

  1. Englert K et al. Symphytum officinale L. Der “Beinwell” in der europaischen Pharmazie und Medizingeschichte. Z Phytother 2005; 26: 158-168.
  2. Predel HG et al. efficacy of a comfrey root extract (Extr. Rad. Symphyti) in the treatment of ankle distortions: results of an observer-blind, randomized, multicenter study. Phytomedicine 2005; 12: 707-714.