Current Medical Research and Opinion® 0300-7995

Vol. 23, No. , 2007, 323–331 doi:10.1185/030079906X167318

© 2007 LibraPharm Limited All rights reserved: reproduction in whole or part not permitted

ORIGINAL ARTICLE

Treatment of acute bronchitis

with a liquid herbal drug
preparation from Pelargonium
sidoides (EPs 7630): a
randomised, double-blind,
placebo-controlled, multicentre
Curr Med Res Opin Downloaded from informahealthcare.com by Gazi Univ. on 12/31/14

study
H. Matthys a and M. Heger b
a
Medical Director emeritus, Department of Pneumology, University Hospital
Freiburg, Freiburg, Germany
b
Clinical Research Department II, Dr. Willmar Schwabe GmbH & Co. KG,
For personal use only.

Karlsruhe, Germany

Address for correspondence: Prof. Dr. med. Heinrich Matthys, Lungs at Home, Hochrüttestr. 17,
D‑79117 Freiburg i. Br, Germany. Tel.: +49‑761‑62822; Fax: +49‑761‑6008580;
email hmatthys@t-online.de
Key words: Acute bronchitis – Bronchitis symptom score – EPs 7630 – Herbal medicine –
Umckaloabo

ABSTRACT

Objective: The objective of this study was to examine the
efficacy and safety of a herbal drug preparation from the roots
of Pelargonium sidoides (EPs* 7630) in the treatment of acute
bronchitis in adults outside the very restricted indication for an
antibiotic therapy.
Research design and methods: This was a randomised, double-
blind, placebo-controlled, multicentre study with 217 patients
aged between 18 and 66 years with acute bronchitis. One
hundred and eight patients were given 30 drops of EPs 7630-
solution three times daily and 109 patients 30 drops of placebo
three times daily for a period of 7 days.
Main outcome measures: Individual change in bronchitis
symptom score (BSS) over 7 days, individual symptoms, patient
satisfaction and adverse events.
Results: After 7 days of treatment, the BSS decreased by
7.6 ± 2.2 points in the EPs 7630 group and by 5.3 ± 3.2 points in
the placebo group. The 95% confidence interval for the difference
between the effects was calculated as 1.6–3.1, showing highly
significant superiority for the EPs 7630 treatment ( p < 0.0001).
There were also marked improvements in the individual
symptoms, which are the components of BSS – cough, chest
pain on coughing, sputum, rales/rhonchi and dyspnoea – in the
treatment group, relative to placebo. Patient satisfaction was very
good. Only minor and transitory adverse events were recorded.
No serious adverse events occurred during the trial.
Conclusion: EPs 7630-solution is a well tolerated and effective
treatment for acute bronchitis in adults outside the very restricted
indication for an antibiotic therapy.

Introduction of cases are due to viral infection, although bacterial

Acute bronchitis is one of the most frequent infections
encountered in general practice and takes top place
in notifications of days off work1,2. The great majority
* EPs is a registered trademark of Dr. Willmar Schwabe GmbH & Co. KG, Germany
infections and allergies may play a role. The pathogen
is often not identified2–4.
Treatment of acute bronchitis is usually symptomatic,
with antipyretics, analgetics, antitussives, or expectorants

Paper 3460 323

 (mucolytics, secretolytics) 3,5. Antibiotics are often
prescribed, but cannot be generally recommended,
unless the acute bronchitis presents as an exacerbation
of chronic bronchitis 6–9. There is little evidence to
support the use of β 2‑agonists in patients without
bronchial obstruction10. In this context, treatment with
EPs* 7630-solution (Umckaloabo†) outside the very
restricted indication for an antibiotic therapy has gained
increasing interest.
EPs 7630-solution is a liquid herbal drug preparation
from the roots of Pelargonium sidoides (1:8–10; extraction
solvent: ethanol 11% [w/w]), widely used in Germany,
the Commonwealth of Independent States, the Baltic
states and in Mexico for the treatment of ear, nose and
throat (ENT) and respiratory tract infections. While the
mechanism of action of EPs 7630 is not fully understood,
anti-microbial11 and immune-modulating effects12 have
been demonstrated for tannins (e.g. catechin) and
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7-hydroxycoumarins (e.g. umckalin). The immune-
modulatory activities are mediated mainly by the release
of tumour necrosis factor‑α (TNF‑α) and nitric oxides
(iNO), the stimulation of interferon‑β (INF‑β) and an
increase in natural killer cell (NK) activity12.
Good results have already been obtained through
observational studies in the treatment of acute
bronchitis in adults and in children13–16. Moreover, in
For personal use only.
a randomized, double-blind, placebo-controlled trial
with 124 adult patients reported by Chuchalin et al.17,
in which the efficacy and safety in the treatment of
acute bronchitis in adults has been evaluated, treatment
with EPs 7630-solution for seven days clearly reduced
bronchitis specific symptoms more effectively and
faster than placebo. Tolerability was rated as good or
very good in more than 95% of patients.
Now, a randomised, double-blind, placebo-controlled,
multicentre trial was conducted to investigate the
efficacy and safety of EPs 7630 in the treatment of
acute bronchitis in a larger trial population.
Methods
Study design
The trial was conducted in Russia as a prospective,
randomised, placebo-controlled, phase IV multicentre
trial with two parallel groups and a group sequential
adaptive design with three interim analyses, to
compare the efficacy and safety of EPs 7630-solution
and placebo in adult patients with acute bronchitis.
Patient were included in a total of six trial sites
consisting of three polyclinics of the Russian State
* EPs is a registered trademark of Dr. Willmar Schwabe GmbH & Co. KG, Germany
† Umckaloabo is a registered trademark of Dr. Willmar Schwabe GmbH & Co. KG, Germany; manufacturer:
ISO-Arzneimittel, Ettlingen, Germany
324 EPs 7630-solution in acute bronchitis
Medical University (RSMU) (Dr. L. A. Kasakitova,
Polyclinic 49, Dr. M. P. Michajlusova, Polyclinic 74,
Dr. N. K. Runichina, Polyclinic 176) and three centres
of the Scientific Research Institute of Pulmonology of
the Ministry of Health and Social Development of the
Russian Federation (M. G. Paschenko, M. O. Potapowa,
L. W. Kisljak), all located in Moscow, Russian Federation.
Enrolment was started as soon as the protocol had been
approved by the ethics committees of the Russian State
Research Institute of Pulmonology in Moscow and
all legal prerequisites had been met. The definition of
the analysis sets for the interim analyses and the final
analysis was made before breaking the blind.
During the enrolment period, the investigators
had to register all screened and suitable patients with
symptoms of acute bronchitis in an electronic database,
including medical histories and the bronchitis symptom
score (BSS) values. Patients fulfilling all inclusion
criteria, not violating any exclusion criteria and giving
informed consent, were allocated, double-blind, to one
of the treatment groups according to a list generated on
a computer by block randomisation. For the patients
who were not enrolled, all reasons were documented.
After inclusion in the trial (on day 0), the baseline
examinations were performed. Follow-up examinations
were scheduled for day 3–5 and day 7. During the
whole trial period the patient had to complete a diary.
Participants
Adult patients with acute bronchitis were included.
As further inclusion criteria, the duration of symptoms
had to be less than 48 hours prior to enrolment into the
trial and the BSS had to be of more than five points.
Exclusion criteria were an indication for antibiotic
treatment (e.g. suspected pneumonia) or treatment
with antibiotics during the 4‑weeks prior to enrolment
in the trial, allergic bronchial asthma, tendency to bleed,
severe heart, renal or liver diseases, immunosuppression,
known or supposed hypersensitivity to trial medication,
concomitant medication that might affect trial results
or interact with the study medication (e.g. antibiotics),
participation in another clinical trial during the
preceding 3 months and patients irresponsible or
unable to understand the nature of the study.
Interventions
Patients were given either 30 drops of EPs 7360 solution
three times daily 30 minutes before or after a meal
for 7 consecutive days, or a matched placebo for the
same period. The patients received the investigational
© 2007 LIBRAPHARM LTD – Curr Med Res Opin 2007; 23()
 medication together with paracetamol tablets (500 mg),
which were allowed in cases of fever ≥ 39°C.
Outcomes
The primary outcome criterion for the efficacy of
EPs 7630-solution compared to placebo was the change
in BSS from day 0 to day 7 of treatment (day 7 minus
day 0). The BSS is based on severity ratings between 0
(absent), 1 (mild), 2 (moderate), 3 (severe) and 4 (very
severe) for the five most important features associated
with acute bronchitis – cough, sputum, rales/rhonchi,
chest pain during coughing and dyspnoea18,19 – and thus
results in a maximum score of 20 points. The last-
observation-carried-forward (LOCF) method was used
when patients discontinued the trial prior to day 7 and
data were therefore missing at day 7.
Secondary outcome measures included the general
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symptoms of an infection – hoarseness, headache, pain
in the limbs, fatigue and fever – which were rated in
an analogous manner to the bronchitis symptoms. The
patients were also asked about their satisfaction with the
treatment, rated according to the Integrative Medicine
Patient Satisfaction Scale (IMPSS). The investigator
was asked to assess the efficacy of the treatment, rated
according to the Integrative Medicine Outcomes Scale
For personal use only.
(IMOS). All parameters were measured at baseline and
at follow-up visits after 3–5 and 7 days of treatment.
Safety outcome criteria were the number, type and
severity of adverse events (AEs) and tolerability, based
on a verbal four-point rating scale.
Sample size
Based on the results of previous studies, the average
decrease in BSS from baseline was expected to be five
points under placebo and seven points with active
treatment. With a sample size of 37 patients in each
treatment group, and an assumed pooled standard
deviation of three points, the trial was estimated to
have a power of 80% for detecting a difference between
groups of two points in BSS relative to baseline (t‑test for
independent samples, α = 0.025, one-sided). The trial
was planned according to a group sequential adaptive
design, with the option of early stopping or continuation
with sample size adjustment after the interim analysis20,21.
Randomisation
All randomisation schedules were prepared centrally
by ClinResearch GmbH, Cologne, Germany, with 90
blocks of four patients. Each study centre was given
six consecutive blocks. The randomisation numbers
corresponded to one of the two possible treatments and
were awarded successively to patients at each centre.
© 2007 LIBRAPHARM LTD – Curr Med Res Opin 2007; 23()
At the baseline examination (day 0), each patient
was to be assigned an individual number (patient
number) by the remote data entry system according
to the randomisation schedule. Patient numbers were
to be assigned consecutively in ascending order in each
study site, starting with the lowest available number at
the respective study site. The lowest available number
was to be given to the first eligible patient; the next
higher number was to be given to the next patient
and so on, in the sequence of their enrolment into the
trial.
Blinding
Placebos were matched to EPs 7630-solution with
respect to colour, smell, taste and viscosity. The
investigators were blinded to the treatments.
Statistical methods
The trial was conducted according to a group sequential
adaptive design with three interim analyses. The
primary efficacy variable was the change in BSS (day
7 minus day 0). The experiment-wise type I error rate
was set at 0.025 (one-sided). The trial was planned
using a group sequential test design within the ∆‑class
of critical values according to Wang and Tsiatis22. The
critical values of the group sequential test design were
calculated for the standardised cumulative test statistic
with the boundary shape parameter ∆ = 0.523. For one-
sided α = 0.025, the resulting adjusted significance levels
at each interim analysis k were given by αk = 0.007907,
with corresponding critical values of Z = 2.413.
For confirmatory testing in the interim analyses, as
well as in the final analysis, an analysis of covariance
was performed, with the factors ‘treatment group’ and
‘centre’ and the baseline value of the primary efficacy
variable as covariate. For estimating the difference of
effects between the two treatment groups (EPs 7630
minus placebo), the 95% two-sided repeated confidence
interval was computed. All analyses of secondary
variables were of a descriptive and exploratory nature
and all analyses were based on intention to treat.
Results
Recruitment and participant flow
The time between the first recruitment and the last
follow-up in the trial was between 2 October 2000 and
19 March 2002. Seven hundred and thirty-five patients
were screened for inclusion into the study; 518 patients
were not randomised because they did not fulfil all
inclusion criteria, violated against an exclusion criterion
EPs 7630-solution in acute bronchitis Matthys and Heger 325
 or because of the absence of the informed consent. Thus
217 patients were included into the study, of which
109 patients were randomly assigned to the placebo
group and 108 to the active treatment group. All of
the randomised patients could be evaluated in the final
intent-to-treat analysis with missing values substituted
by application of the LOCF method. Between day 0
and day 3–5, only one patient withdrew from the
active treatment group. At the follow-up on day 3–5,
four patients (4/107, 3.7%) withdrew from the active
treatment group and 12 patients (12/109 [11.0%])
from the placebo group, in the latter predominantly
because of lack of efficacy (eight patients). One patient
withdrew from each group between the visit at days 3–
5 and the final visit at day 7, leaving 102 patients in the
active treatment group and 96 patients in the placebo
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group for the observed cases analysis evaluation. The
participant flow is summarised in Figure 1.
Baseline data
Of the 217 randomised patients, 53 (24.4%) were
male and 164 (75.6%) female. There were slightly
more females in the placebo group (86 [78.9%]) than
in the treatment group (78 [72.2%]). The age of the
patients ranged between 18 and 66 years, with a mean
(SD) of 37.4 ± 12.4 years. The mean body weight was
72.8 ± 14.1 kg.
Current smokers could be found in the treatment
group (23 [21.3%]) as well as in the placebo group (27
[24.8%]). There were slightly more former smokers in
the treatment group (16 [14.8%]) than in the placebo

Not randomised,
Screened, nn=735
Screened, = 735
nn=518
= 518

Randomised, nn=217
Randomised, = 217
For personal use only.

EPs 7630 Placebo

Day 0 Day 0
nn=108
= 108 nn=109
= 109

Withdrawal
Withdrawal
n=
n=1
1
Reason:
• Other, n = 1

Withdrawal
Withdrawal Days
Day 3-5
3–5 Days
Day 3•5
3–5 Withdrawal
n =n=4
4 nn=107
= 107 nn=109
= 109 nn=12
= 12
Reasons: Reasons:
• Free of symptoms, n = 1 • Lack of efficacy, n = 8
• AE, n = 1 • Free of symptoms, n = 1
• Free of symptoms and AE, n = 1 • AE, n = 1
• Other, n = 1 • Lack of efficacy and AE, n = 2

Withdrawal
Withdrawal Withdrawal
n =n=1
1 nn=1
=1
Reason: Reason:
• AE, n = 1 • AE, n = 1

Day 7 Day 7
n = 102
n=102 nn=96
= 96

Figure 1. Disposition of patients in the study. AE = adverse event

326 EPs 7630-solution in acute bronchitis © 2007 LIBRAPHARM LTD – Curr Med Res Opin 2007; 23()
 group (12 [11.0%]). The majority of patients never
smoked; 69/108 (63.9%) in the treatment group and
70/109 patients (64.2%) in the placebo group.
ENT operations, mostly tonsillectomy and
adenotomy, were reported for 18/108 patients (16.7%)
in the active treatment group and 13/109 patients
(11.9%) in the placebo group. Previous ENT infections,
usually rhino­pharyngitis and bronchitis, were reported
by the majority of patients; 101/108 (93.5%) in the
active treatment group and 104/109 (95.4%) in the
placebo group.
Concomitant diseases were reported by 48/108
patients (44.4%) in the active treatment group and
43/109 patients (39.4%) in the placebo group. Cardio­
vascular disorders were reported for 27/108 patients
(25.0%) in the active treatment group and in 18/109
(16.5%) of the patients in the placebo group. Gastro­
intestinal disorders were reported in 14/108 patients
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(13.0%) in the active treatment group and 17/109
patients (15.6%) in the placebo group.
Concomitant medication was taken during the trial by
17/108 patients (15.7%) in the active treatment group
and 12/109 patients (11.0%) in the placebo group.
These were almost exclusively standard cardiovascular
drugs, including calcium antagonists, β‑blockers and
ACE inhibitors. There was no difference between the
For personal use only.
groups with respect to standard laboratory parameters
(leuko­cyte count, erythrocyte sedimentation rate,
transaminases, clotting parameters).
At baseline the overall mean ± SD (median) BSS
was 8.6 ± 1.7 (8.0) points; placebo, 8.4 ± 1.8 (8.0)
points; EPs 7630, 8.9 ± 1.6 (9.0) points. At baseline,
all patients suffered from cough.
10
8
Bronchitis symptom scale
4
Placebo
EPs 7630
0
Day 0
Figure 2. Bronchitis-specific symptoms score (BSS) at different visits for the two treatment groups (mean ± 95% confidence
interval): placebo (n = 109); EPs 7630 (n = 108)
© 2007 LIBRAPHARM LTD – Curr Med Res Opin 2007; 23()
Outcomes
Figure 2 shows the BSS scores for both treatment groups
for the three different visits. At day 0, BSS was 8.9 ± 1.6
points for the treatment group and 8.4 ± 1.8 points
for the placebo group. At the first follow-up visit (day
3–5), BSS decreased to 4.2 ± 2.0 points in the treatment
group and 5.9 ± 2.5 points in the placebo group. By day
7, BSS was 1.3 ± 2.1 points in the treatment group and
3.1 ± 3.0 points in the placebo group.
The primary outcome measure was the individual
difference of the BSS between day 0 and day 7. The
decrease was more pronounced in the active treatment
group, with 7.6 ± 2.2 (8.0) points, than in the placebo
group, with a value of 5.3 ± 3.2, (6.0) points. This
difference was statistically significant when applying a
two-factorial analysis of covariance as specified above
( p < 0.0001). The 95% confidence interval for the
difference between the BSS was calculated as 1.6–3.1,
showing the relevant treatment effect of the EPs 7630
treatment.
Figure 3 illustrates that 45.4% of the patients on
active treatment were assessed by the physician as
having experienced complete recovery at day 7, in
comparison with 6.4% of patients on placebo; 89.8%
of patients on active treatment reported complete
recovery or major improvement, in comparison with
65.1% of patients on placebo.
In Table 1 and Figure 4, the effects of treatment on
the component symptoms of BSS are summarised. As
shown in Table 1, the percentage of patients reporting
complete remission was larger with EPs 7630-solution
for each of the five component symptoms.
Day 3 to 5 Day 7
EPs 7630-solution in acute bronchitis Matthys and Heger 327
 70

60

50

Percentage of patients
Placebo
EPs 7630
40

30

20

10

0
Complete Major Slight No change Deterioration No remark
recovery improvement improvement
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Figure 3. Treatment outcomes assessed by investigator for the two treatment groups: placebo (n = 109);
EPs 7630 (n = 108); measured at day 7

100
Improvement
Remission

80
Percentage of patients
For personal use only.

60

40

20

0
Placebo EPs 7630 Placebo EPs 7630 Placebo EPs 7630 Placebo EPs 7630 Placebo EPs 7630
Cough Sputum Rales/rhonchi Chest pain on coughing Dyspnoea

Figure 4. Remission and improvement rates from baseline to last observation for bronchitis-specific symptoms (see Table 1)

Table 1. Effect of EPs 7630 treatment on the individual In the active treatment group, 92.6% of patients
symptoms of bronchitis at day 7. Comparison between (100/108 patients) reported complete remission or
EPs 7630 and placebo marked improvement in cough, in comparison with
86.2% (94/109 patients) receiving placebo treatment
(Figure 4). Five out of 109 patients (4.6%) reported
Symptom Patients reporting complete remission ,
% (n/N)* deterioration under placebo, in comparison with none
under active treatment.
EPs 7630 Placebo
Sixty-seven out of 82 patients with non-missing
Cough 51.9 (56/108) 11.9 (13/109)
values (81.7%) on active treatment reported complete
Sputum 68.3 (56/82) 40.0 (34/85) re­mission or marked improvement in sputum
Rales/rhonchi 88.2 (82/93) 50.0 (44/88) production, in comparison with 62.4% (53/85 patients)
Dyspnoea 87.9 (80/91) 76.7 (66/86) during placebo treatment; 5/85 patients (5.9%)
Pain on coughing 93.4 (99/106) 86.0 (86/100) reported deterioration under placebo, in comparison
*Percentage of patients reporting complete remission (number of
with none under active treatment.
patients with complete remission/total number of patients with Complete remission or marked improvement in
non-missing values) rales/rhonchi was reported for 94.6% of patients (88/93

328 EPs 7630-solution in acute bronchitis © 2007 LIBRAPHARM LTD – Curr Med Res Opin 2007; 23()
 patients) on active treatment, in comparison with
65.9% (58/88 patients) during placebo treatment; 5/88
patients (5.7%) reported deterioration under placebo,
in comparison with none under active treatment.
Table 2 summarises the effect of treatment on
the individual symptoms of infection. The same
data are illustrated in Figure 5. The percentage of
patients reporting complete remission was larger with
active treatment for each of the five component
symptoms.
With regard to hoarseness, 95.0% of patients (95/100
patients) on active treatment reported complete
remission or marked improvement, in comparison
with 76.6% (72/94 patients) during placebo treatment
(Figure 5); 2/94 (2.1%) patients reported deterioration
under placebo, in comparison with none under active
treatment.
For headache, 95.9% of patients (94/98 patients)
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88.3% (83/94 patients) during placebo treatment;
3/94 (3.2%) patients reported deterioration under
placebo, in comparison with none under active
treatment.
Complete remission or marked improvement in
fatigue was reported in 93.5% of patients (101/108
patients) on active treatment, in comparison with
84.3% (91/108 patients) during placebo treatment;
2/108 patients (1.9%) reported deterioration under
placebo, in comparison with none under active
treatment.
Figure 6 compares the patient satisfaction with the
two treatments. In total, 84.3% of the patients (91/108
patients) were very satisfied or satisfied with the active
treatment, in comparison with 47.7% (52/109 patients)
on placebo.
Adverse events

on active treatment reported complete remission

or marked improvement, in comparison with No serious AEs were recorded during the study.
A total of 47/217 patients (21.7%) experienced at
Table 2. Effect of EPs 7630 treatment on the individual least one AE during the trial, 23/108 patients (21.3%)
symptoms of general infection at day 7. Comparison in the active treatment group and 24/109 patients
between EPs 7630 and placebo (22.0%) in the placebo group. In both treatment
groups, the system organ classes (SOC) most frequently
Symptom Patients reporting complete remission , coded were ‘investigations’ and ‘blood and lymphatic
For personal use only.

% (n/N)*
disorders’, which included laboratory abnormalities.
EPs 7630 Placebo Among these, an increase in the erythrocyte
Hoarseness 80.0 (80/100) 56.4 (53/94) sedimentation rate (EPs 7630, 10/108 patients
Headache 87.8 (86/98) 68.1 (64/94) [9.3%]; placebo, 10/109 patients [9.2%]) and changes
Fatigue 79.6 (86/108) 47.2 (51/108) in leucocyte count (EPs 7630, 4/108 patients
Fever 97.5 (78/80) 91.1 (72/79) [3.7%]; placebo, 5/109 patients [4.6%]) were
Limb pain 93.3 (98/105) 87.6 (85/97) particularly frequent, which are due to the
underlying infectious disease. The number of AEs
*Percentage of patients reporting complete remission (number
of patients with complete remission/total number of patients per SOC did not differ substantially between the two
with non-missing values) treatment groups.

Improvement
Remission
100

80
Percentage of patients

60

40

20

0
Placebo EPs 7630 Placebo EPs 7630 Placebo EPs 7630 Placebo EPs 7630 Placebo EPs 7630
Hoarseness Headache Fatigue Fever Limb pain

Figure 5. Remission and improvement rates from baseline to last observation for non-specific symptoms (see Table 2)

© 2007 LIBRAPHARM LTD – Curr Med Res Opin 2007; 23() EPs 7630-solution in acute bronchitis Matthys and Heger 329
 60
50
Percentage of patients
40
30
20
10
0
Very satisfied
Figure 6. Patient satisfaction with the two treatments: placebo (n = 109); EPs 7630 (n = 108)
Curr Med Res Opin Downloaded from informahealthcare.com by Gazi Univ. on 12/31/14
Discussion
The present paper reports a randomised, double-blind,
placebo-controlled, multicentre study on the efficacy
and safety of the herbal medicine EPs 7630-solution in
the treatment of acute bronchitis in adults. The primary
For personal use only.
outcome measure was the individual difference in the
BSS, which scores the five most important features of
acute bronchitis, namely cough, sputum, rales/rhonchi,
chest pain during coughing and dyspnoea18,19, between
day 0 and day 7. The 95% confidence interval for the
difference between the effects was calculated as 1.6–
3.1, demonstrating the significant statistical and clinical
superiority of EPs 7630-solution in the treatment of
patients with acute bronchitis.
Because the number of dropouts was higher in
the placebo group, which can contribute to a larger
treatment effect when applying LOCF, we analysed
the effect of various replacement methods beside the
LOCF method on the difference in treatment effects.
The methods used were best/worst observation carried
forward, replacement by the mean of all patients and
of all patients of the corresponding treatment group,
the value ‘0’, the Diggle/Kenward dropout model24
and the very conservative method of replacing missing
values in the EPs 7630 group by the worst and in the
placebo group by the best value. Efficacy analysis was
also performed by using observed cases only. Each of
these methods revealed highly statistically significant
treatment effects ( p‑values < 0.0001) as found with the
LOCF method with somewhat smaller but comparable
differences between the treatment groups.
Especially marked were the treatment effects on
the bronchitis-symptoms fatigue, rales/rhonchi and
cough. The difference between active treatment and
330 EPs 7630-solution in acute bronchitis
Placebo
EPs 7630
Satisfied Undecided Dissatisfied Very dissatisfied No remark
placebo for the symptoms chest pain on coughing and
dyspnoea were smaller than for the other symptoms, as
these symptoms usually tend to be more self-limiting,
irrespective of treatment. This also applies to the
difference between active treatment and placebo for
the individual infection-symptoms limb pain and fever.
It is also notable that deterioration in symptoms was
found occasionally in the patient treated with placebo,
but never with EPs 7630. Moreover, patient satisfaction
with EPs 7630-solution was very good.
As the definition of acute bronchitis is still under
discussion, diagnosis is solely based on clinical findings,
without standardized diagnostic signs and sensitive
or specific confirmatory laboratory tests 25. Due to
this lack in standardized criteria, which makes the
development of commonly accepted diagnostic criteria
highly desirable, all outcomes applied in this study are
self-report.
The results of this study indicate that treatment
with EPs 7630 markedly improved the symptoms of
adult patients suffering from acute bronchitis. This
is in accordance with an earlier randomised, double-
blind, placebo-controlled trial with a total (ITT) of
124 patients reported by Chuchalin et al.17, in which
the mean decrease in BSS score during 7 days was
7.2 ± 3.1 points in the EPs 7630 group and 4.9 ± 2.7
points in the placebo group, which is compatible
with the current findings. Moreover, in both studies
EPs 7630-solution was well tolerated with no serious
AEs reported and a comparable AE rate in both trials;
thus the results reported by Chuchalin et al.17 could be
confirmed by the present study consisting of a larger
trial population. A comparable good tolerability was
also found in several observational studies in both
adults and children with acute bronchitis13–16.
© 2007 LIBRAPHARM LTD – Curr Med Res Opin 2007; 23()
 Conclusion
The results of this trial demonstrate that EPs 7630-
solution is an effective and well tolerated herbal
medicine in the treatment of acute bronchitis in adult
patients outside the strict indication for an antibiotic
therapy.
Acknowledgement
Declaration of interest: The study was commissioned
and financially supported by ISO-Arzneimittel,
Ettlingen, Germany.
Data management and statistical analyses were
prepared centrally by ClinResearch GmbH, Cologne,
Germany.
We thank the following investigators without
Curr Med Res Opin Downloaded from informahealthcare.com by Gazi Univ. on 12/31/14
whose help the study could not have been performed:
Dr. L. A. Kasakitova (Polyclinic 49, Russian State
Medical University, Moscow), Dr. M. P. Michajlusova
(Polyclinic 74, Russian State Medical University,
Moscow), Dr. N. K. Runichina (Polyclinic 176, Russian
State Medical University, Moscow), M. G. Paschenko
(Scientific Research Institute of Pulmonology,
Moscow), M. O. Potapowa (Scientific Research
For personal use only.
Institute of Pulmonology, Moscow) and L. W. Kisljak
(Scientific Research Institute of Pulmonology,
Moscow). We also thank all study participants for
volunteering to participate in this study.
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