Reviewed: Kamin W, Ilyenko LI, Malek FA, Kieser M. Treatment of acute bronchitis with EPs 7630; a randomized, controlled trial in children and adolescents. Pediatr Int. 2012;54(2):219-226.

Acute bronchitis is a common childhood illness. Although 95% of the cases are caused by viruses, about one-third of patients are prescribed antibiotics. Studies have shown that antibiotic therapy is mostly ineffective in acute bronchitis, unless the pathogen is of bacterial origin and known by lab test. A therapeutic alternative in the first-line treatment of acute bronchitis is EPs 7630 (the active ingredient of the product Umckaloabo^®; ISO Arzneimittel; Ettlingen, Germany), which has been approved in Germany for use in children aged 1 year and older and in adults. EPs 7630 is an herbal drug preparation from the roots of Pelargonium sidoides (Geraniaceae) (1:8-10; extraction solvent: ethanol 11% [w/w]). These authors conducted a randomized, double-blind, placebo-controlled clinical trial to demonstrate the efficacy and tolerability of EPs 7630 in children and adolescents suffering from acute bronchitis.

The pharmacological activities of EPs 7630 and its components, which include antibacterial potencies and immune modulatory capabilities, have been demonstrated in vitro. The immunomodulatory activities are mainly mediated by the release of tumor necrosis factor-alpha and nitric oxides, the stimulation of interferon-beta, and the increase in natural killer cell activity.^1-4

This study was conducted between March and May 2006 in 11 Russian pediatric centers. Patients who met the inclusion criteria were randomly allocated to one of 2 treatment groups. Following a baseline examination and subjective evaluations, the patients were scheduled for follow-up examinations on days 3-5 (visit 2) and day 7 (visit 3).

To be included, the patients had to be aged 1 to 18 years and suffering from acute bronchitis with symptoms starting ≤ 48 hours before inclusion in the study and a total score of bronchitis-specific symptoms (BSS) ≥ 5 points at the time of screening.

A total of 220 patients were randomized to receive EPs 7630 (n=111) or placebo (n=109) as follows: 10 drops 3 times daily for patients aged 1 to 6 years; 20 drops 3 times daily for patients aged > 6 to 12 years; or 30 drops 3 times daily for patients aged > 12 to 18 years for 7 consecutive days.

No significant differences were noted at baseline between the groups for demographic and anthropometric data. Concomitant medication was taken by 6.3% of patients in the EPs 7630 group and 10.1% in the placebo group. Acetaminophen use was allowed and did not differ between groups. Antibiotics were taken by 5 patients in the EPs 7630 group and 3 patients in the placebo group.

The primary efficacy variable was the change in the BSS total score from day 0 to day 7. The BSS total score comprised 3 items, including: “coughing,” “pulmonary rales at auscultation” (crackling sounds during breathing heard with a stethoscope), and “dyspnea.” At each visit, those symptoms were scored according to a 5-point verbal rating scale from 0 (“not present”) to 4 (“very severe”).

From baseline to day 7, the mean BSS total score decreased by 4.4±1.6 points in the EPs 7630 group compared with 2.9±1.4 points in the placebo group.

A continuous decrease in the mean BSS total score between baseline and day 7 was observed in both groups, but scores were significantly better with EPs 7630 than placebo after 3-5 and 7 days: EPs 7630 versus placebo day 0: 6.0±1.6 vs. 5.8±1.3; day 3-5: 3.6±1.4 vs. 4.3±1.4; day 7: 1.6±1.4 vs. 2.9±1.4 (P<0.0001 for days 3-5 and day 7, respectively).

For individual symptoms, “coughing” and “pulmonary rales at auscultation,” the mean decrease in BSS between day 0 and day 7 was more pronounced in the EPs 7630 group compared with the placebo group (P<0.0001). “Dyspnea” (difficult breathing; shortness of breath) showed a nonsignificant advantage for EPs 7630.

Regarding general symptoms, “lack of appetite” was significantly improved in the EPs 7630 group (P=0.0003) at day 7.

Among other secondary efficacy variables were the response rates defined as BSS total score of < 3 points at day 7 (criterion 1); decrease in BSS total score by at least 4 points from day 0 to day 7 (criterion 2); and BSS total score < 3 at day 7 combined with a decrease in BSS total score by at least 4 points from day 0 to day 7 (criterion 3).

Response rates at day 7 were considerably higher in the EPs 7630 group compared with the placebo group. For all 3 response criteria, a statistically significant difference was observed for the EPs 7630 group (P<0.0001 for each).

The treatment effect occurred significantly earlier in the EPs 7630 group compared with the placebo group (P<0.0001).

Evaluation of treatment outcome by the investigator and satisfaction of patients with treatment were each significantly better in the EPs 7630 group compared with the placebo group (P<0.0001 for both).

Three adverse events were observed in two of the 111 patients in the EPs 7630 group, but a causal relationship was excluded in all 3 cases. Clinical laboratory parameters showed only marginal group differences.

These results support the efficacy, tolerability, and safety of the herbal drug preparation EPs 7630 in children and adolescents aged 1-18 years suffering from acute bronchitis. This confirms a previously published observational study in children ages 0-12 years.⁵

According to the authors, the treatment benefit was most pronounced for the symptoms “coughing” and “rales on auscultation,” which could be explained by the improvement of ciliary beating as found in vitro.6 They suggest that this could be an important mode of action independent of antibacterial activity as most episodes of acute bronchitis are caused by viruses, as previously noted.

The authors point out that even in diseases requiring antimicrobial therapy, initial treatment with EPs 7630 could “bridge the time between presentation of the patient and the final decision on an appropriate antibiosis, thus reducing the risk of uncritical antibiotic treatment.”

A previous systematic review of 6 clinical trials on EPs 7630 used by patients with bronchitis concluded there is “encouraging evidence from currently available data that P. sidoides is effective compared to placebo for patients with acute bronchitis.”⁷

This study was supported by Schwabe Pharmaceuticals, Karlesruhe, Germany.

—Shari Henson

References

1. Kayser O, Kolodziej H, Kiderlen AF. Immunomodulatory principles of Pelargonium sidoides. Phytother Res. 2001;15(2):122-126.
2. Kolodziej H. Fascinating metabolic pools of Pelargonium sidoides and Pelargonium reniforme, traditional and phytomedicinal sources of the herbal medicine Umckaloabo^®. Phytomedicine. 2007;14(suppl VI):9-17.
3. Kolodziej H, Kayser O, Radke OA, Kiderlen AF. Pharmacological profile of extracts of Pelargonium sidoides and their constituents. Phytomedicine. 2003;10(suppl IV):18-24.
4. Kolodziej H, Kiderlen AF. In vitro evaluation of antibacterial and immunomodulatory activities of Pelargonium reniforme, Pelargonium sidoides and the related herbal drug preparation EPs^® 7630. Phytomedicine. 2007;14(suppl VI):18-26.
5. Minigh J. Pelargonium sidoides as a treatment for acute bronchitis in children. HerbClip. February 15, 2008 (No. 050273-346) Austin, TX: American Botanical Council. Review of Treatment effect and safety of EPs^® 7630-solution in acute bronchitis in childhood: Report of a multicentre observational study by Haidvogl M, Heger M. Phytomedicine. 2007;14(Suppl.VI):60-64.
6. Neugebauer P, Mickenhagen A, Siefer O, Walger M. A new approach to pharmacological effects on ciliary beat frequency in cell cultures – exemplary measurements under Pelargonium sidoides extract (EPs 7630). Phytomedicine. 2005;12(1-2):46-51.
7. Agbabiaka TB, Guo R, Ernst E. Pelargonium sidoides for acute bronchitis: a systematic review and meta-analysis. Phytomed. 2008;15(5):378-385.