Reviewed: Matthys H, Lizogub VG, Malek FA, Kieser M. Efficacy and tolerability of EPs 7630 tablets in patients with acute bronchitis: a randomised, double-blind, placebo-controlled dose-finding study with a herbal drug preparation from Pelargonium sidoides. Curr Med Res Opin. April 15, 2010; [Epub ahead of print]. doi:10.1185/03007991003798463.

Up to 95% of acute bronchitis cases may be viral, yet antibiotics continue to be frequently prescribed. Clinical trials have demonstrated that the hydroalcoholic extract from the roots of Pelargonium sidoides (Geraniaceae) EPs 7630, which is the active ingredient in Umckaloabo® (ISO Arzneimittel, Ettlingen, Germany; imported into the United States as Umcka® by Nature’s Way, Springville, UT) is effective in treating acute bronchitis in adults, infants, and children.^1,2 In vitro studies have demonstrated moderate direct antibacterial activity, enhanced phagocytosis, improved ciliary beating, and immunomodulatory effects for the extract. Prior clinical trials have used liquid EPs 7630 formulations. The purpose of this prospective, double-blind, placebo-controlled dose-finding clinical trial “was to investigate the efficacy and tolerability of EPs 7630 administered as tablets in the treatment of adults suffering from acute bronchitis.”

This clinical trial was conducted at 16 study centers in the Ukraine between February and April 2006. EPs 7630 extract consisted of a dried 11% w/w ethanolic root extract (1:8-10). The patients were randomized using a computer-generated randomization list to a placebo group or 1 of 3 treatment groups: 30, 60, or 90 mg EPs 7630/day. Following a screening visit, the patients took their assigned treatment 30 minutes before meals 3 times daily for 8 days.

The primary efficacy measure was the change in the total bronchitis-specific symptoms (BSS) score from day 0 to day 7 as rated by an investigator. The BSS total score consists of 5 bronchitis symptoms rated on a scale of 0 (not present) to 4 (very severe): coughing, sputum, pulmonary rales at auscultation (an abnormal bubbling sound in the chest caused by mucous build-up, heard with a stethoscope), chest pain while coughing, and dyspnea (shortness of breath). Patients and investigators completed the Integrative Medicine Outcome Scale (IMOS), which rates the treatment outcome on a scale from 1 (complete recovery) to 5 (deterioration). The SF-12 Health Survey and EQ-5D were used to assess health-related quality of life. The Integrative Medicine Patient Satisfaction Scale (IMPSS) was used to assess the patients’ satisfaction with treatment from 1 (very satisfied) to 5 (very dissatisfied). The researchers assessed further parameters, including laboratory safety parameters, adverse events, acetaminophen use, inability to work, and change of general symptoms. The patients were over 18 years of age and had been suffering from acute bronchitis starting 48 hours or less prior to inclusion into the study. They were allowed to take no more than 1,500 mg acetaminophen per day.

Out of 406 patients who were randomized, 405 were included in the full analysis set. The per protocol set included 404 patients because 1 patient in the 30 mg EPs 7630 group took a forbidden concomitant medication. The full analysis set included 102 patients in the placebo group, 102 patients in the 30 mg EPs 7630 group, 101 patients in the 60 mg EPs 7630 group, and 100 patients in the 90 mg EPs 7630 group. There was 1 withdrawal in the placebo group (lack of efficacy), 2 withdrawals in the 30 mg group (other reason, forbidden concomitant medication), and 1 withdrawal in the 90 mg group (adverse event).

The total BSS score decreased from day 0 to day 7 by 2.7 ± 2.3 (mean ± standard deviation) in the placebo group, 4.3 ± 1.9 in the 30 mg group, 6.1 ± 2.1 mg in the 60 mg group, and 6.3 ± 2.0 in the 90 mg group (P<0.0001 placebo vs. 30 mg, 60 mg, and 90 mg EPs 7630 groups). The total BSS score was also significantly lower in the 30, 60, and 90 mg EPs 7630 groups compared to the placebo group at days 3-5 (P<0.0001 for all active treatment groups compared to placebo), and the difference increased in a dose-dependent manner through day 7. The authors write that the decrease in the total BSS score was significantly greater in the 60 mg group compared to the 30 mg group (P value not given). At day 7, the total BSS score was below 3 points for 5.9% of the placebo group patients and for 24.5% of the 30 mg group, 57.4% of the 60 mg group, and 55.0% of the 90 mg group (P=0.0002 placebo vs. 30 mg, P<0.0001 for placebo vs. 60 and 90 mg groups). The total BSS score decreased by at least 7 points from day 0 to day 7 for 6.9% of the placebo group patients and 14.7%, 43.6%, and 46.0% of the patients in the 30, 60, and 90 mg EPs 7630 groups, respectively (P<0.0001 for placebo vs. 60 and 90 mg EPs 7630 groups). The reduction in the intensity of the individual BSS symptoms increased with increasing EPs 7630 dose (P<0.0001 for all). The reductions in coughing and pulmonary rales at auscultation from day 0 to day 7 were significantly greater in each of the EPs 7630 groups compared to the placebo group (P<0.0001 for all). The reductions in sputum, chest pain while coughing, and dyspnea were greater in the 60 and 90 mg groups compared to the placebo group (P<0.0001).

Patients in the EPs 7630 groups experienced dose-dependent decreases from day 0 to day 7 in hoarseness, headache, limb pain, and fatigue/exhaustion (P=0.0006, P=0.0001, P=0.032, and P=0.0001, respectively). Both the patients’ and investigators’ IMOS ratings were better in all 3 EPs 7630 groups compared to the placebo group (P<0.0001 for all). In the placebo group, 10.8% of patients had completely recovered or had major improvement ratings, while 39.2%, 69.3%, and 77.0% of the 30, 60, and 90 mg EPs 7630 groups, respectively, had completely recovered or achieved major improvement ratings. The patients in all 3 EPs 7630 groups experienced earlier onsets of treatment effect compared to the placebo group (P<0.0001 for all). The median duration of inability to work was 8 days in the placebo group and 6 days in all 3 of the EPs 7630 groups (P<0.0001 for all). The EPs 7630 groups experienced shorter durations of activity limitation during the treatment period than the placebo group (P<0.0001 for all). The physical component score of the SF-12 improved to a greater degree in the EPs 7630 groups compared to the placebo group (P<0.0001 for all). The overall SF-12 score improved to a greater degree in all 3 EPs 7630 groups compared to the placebo group (P<0.0001 for all). The IMPSS scores showed that the EPs 7630 groups were more satisfied with the treatment than the placebo group patients (P<0.0001 for all). There were no significant changes in laboratory safety parameters. The majority of patients (97.8%) took their treatments as prescribed, with no significant differences in compliance rates between the groups. There were 92 mild-to-moderate adverse events in 18.5% of patients during the study, and most were gastrointestinal complaints. The incidence of gastrointestinal disorders was dose dependent, with 4.9% in the 30 mg group, 8.9% in the 60 mg group, and 14.9% in the 90 mg group. No serious adverse events occurred.

These results are in alignment with other clinical trials that have shown liquid EPs 7630 to be effective in treating acute bronchitis. The authors conclude that the “60 mg EPs 7630 daily constitutes the optimal dose with respect to the benefit-risk ratio of EPs 7630 tablets.” Since “a useful alternative for the treatment of acute bronchitis outside the strict indication for antibiotic use is expedient,” EPs 7630 could be considered as a safe and effective means of reducing unnecessary antibiotic use and/or public health system and sick leave costs.