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Pelargonium sidoides extract for treating acute respiratory tract infections

  1. Antje Timmer1,*,
  2. Judith Günther2,
  3. Edith Motschall3,
  4. Gerta Rücker3,
  5. Gerd Antes3,
  6. Winfried V Kern4

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 22 OCT 2013

Assessed as up-to-date: 23 APR 2013

DOI: 10.1002/14651858.CD006323.pub3


How to Cite

Timmer A, Günther J, Motschall E, Rücker G, Antes G, Kern WV. Pelargonium sidoides extract for treating acute respiratory tract infections. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD006323. DOI: 10.1002/14651858.CD006323.pub3.

Author Information

  1. 1

    Leibniz Institute for Prevention Research and Epidemiology - BIPS GmbH, Clinical Epidemiology, Bremen, Germany

  2. 2

    Pharmafacts GmbH - Research and Consulting in Drug Care, Freiburg, Germany

  3. 3

    Institute of Medical Biometry and Medical Informatics, University Medical Center Freiburg, German Cochrane Centre, Freiburg, Germany

  4. 4

    Center for Infectious Diseases and Travel Medicine, University Hospital, Department of Medicine, Freiburg, Germany

*Antje Timmer, Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology - BIPS GmbH, Achterstrasse 30, Bremen, 28359, Germany. timmer@bips.uni-bremen.de.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 22 OCT 2013

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Characteristics of included studies [ordered by study ID]
Bachert 2009

MethodsRCT, double-blind, multi-center


Participants103 adults, acute bacterial sinusitis, diagnosis confirmed by radiography
Setting: ENT clinics and outpatient departments, Ukraine


InterventionsP. sidoides (alcoholic root extract) 3 x 60 drops versus placebo for 21 days


OutcomesPrimary: difference in symptom score change at day 7
Secondary: change in individual symptom severity at day 7 and 21. Quality of life measures, physician assessment (IMOS). Adverse effects


NotesDetails on blocking/treatment assignment clarified by investigator; missing data supplied by investigator
Quality assessment: Grade B (moderate risk of bias)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomization list with balanced block randomization, p.53

Allocation concealment (selection bias)Low riskThe block length was not known to the investigator. Each investigator received a set of blocks with correspondingly numbered study medication. Eligible patients were sequentially allocated to a patient number in ascending order on entry in the trial, p.53

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble-blinding, integrity of blinding not assessed, p.53

Incomplete outcome data (attrition bias)
All outcomes
Low riskFlow chart provided, minimal withdrawal (0/51, 1/52), ITT, p.53

Selective reporting (reporting bias)Unclear riskPrimary outcome reported but not relevant to review, additional outcome information provided as requested

Validated outcome assessment
All outcomes
Unclear riskUnvalidated score used for reporting, additional information supplied (assumes score = 0 for absence of symptoms)

Chuchalin 2005

MethodsRCT, double-blind, multi-center


Participants124 adults, acute bronchitis, < 48 hours past onset
Setting: GP practices, Russia


InterventionsP. sidoides (alcoholic root extract) 3 x 30 drops versus placebo for 7 days


OutcomesPrimary: difference in symptom score change at day 7
Secondary: change in individual symptom severity. Patient satisfaction (IMPSS), physician assessment (IMOS). Adverse effects


NotesDetails on treatment assignment clarified by investigator; missing data supplied by investigator


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskList generated on a computer, p.438

Allocation concealment (selection bias)Low riskResearch staff blinded to treatment allocation, p.438

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble-blinding, integrity of blinding not assessed, p.438 and investigator information

Incomplete outcome data (attrition bias)
All outcomes
Low riskFlow chart provided, low non-differential withdrawal (3/64, 4/60), ITT analysis, p.439

Selective reporting (reporting bias)Unclear riskPrimary outcome reported but not relevant to review, additional outcome information provided as requested

Validated outcome assessment
All outcomes
Unclear riskUnvalidated score used for reporting, additional information supplied (assumes score = 0 for absence of symptoms)

Kamin 2010a

MethodsRCT, double-blind, multi-center


Participants200 children (1 to 18 years), acute bronchitis, < 48 hours past onset
Setting: in- and outpatient departments, Russia


InterventionsP. sidoides (alcoholic root extract) 3 x 10 to 30 drops (depending on age of child) versus placebo for 7 days


OutcomesPrimary: difference in symptom score change at day 7
Secondary: change in individual symptom severity. Patient satisfaction (IMPSS), physician assessment (IMOS). Adverse effects


NotesUnvalidated score used for reporting, additional information supplied (assumes score = 0 for absence of symptoms). Interim report was provided for 2008 version of review by the investigator (Schwabe Pharmaceuticals). Full paper published preceding current update


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random list, p.185

Allocation concealment (selection bias)Low riskConcealed block size, concealed allocation, p.185

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble-blinding, integrity of blinding not assessed, p.185 and investigator information

Incomplete outcome data (attrition bias)
All outcomes
Low riskFlow chart provided, low withdrawal (0/103, 3/97), ITT analysis, p.186

Selective reporting (reporting bias)Unclear riskPrimary outcome reported but not relevant to review, additional outcome information provided as requested

Validated outcome assessment
All outcomes
Unclear riskUnvalidated score used for reporting, additional information supplied (assumes score = 0 for absence of symptoms) score used for reporting, additional information supplied but assumes BSS = 0 for absence of symptoms

Kamin 2010b

MethodsDose-finding RCT (3 treatment arms), double-blind, multi-center


Participants405 children (6 to 18 years), acute bronchitis, < 48 hours past onset
Setting: in- and outpatient departments, Ukraine


InterventionsP. sidoides 3 x 10/20/30 mg tablets versus placebo for 7 days


OutcomesPrimary: difference in symptom score change at day 7
Secondary: change in individual symptom severity. Patient satisfaction (IMPSS), physician assessment (IMOS). Adverse effects


NotesInterim report was provided for 2008 version of review by the investigator (Schwabe Pharmaceuticals). Full paper published preceding current update. For analysis, this study is divided into 3 parts (1 treatment arm, 1/3 of control numbers and control events)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random list, p.538

Allocation concealment (selection bias)Low riskInvestigator supplied information, p.538

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble-blinding, integrity of blinding not assessed, p.537, and investigator supplied

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskOverall 1 drop-out (?), no flow chart

Selective reporting (reporting bias)Unclear riskPrimary outcome reported but not relevant to review, additional outcome information provided as requested, p.435 and 560

Validated outcome assessment
All outcomes
Unclear riskUnvalidated score used for reporting, additional information supplied (assumes score = 0 for absence of symptoms)

Kamin 2010b - 10 mg

MethodsDose-finding RCT (first of 3 treatment arms), double-blind, multi-center


ParticipantsChildren (6 to 18 years), acute bronchitis, < 48 hours past onset
Setting: in- and outpatient departments, Ukraine


InterventionsP. sidoides 3 x 10 mg tablets versus placebo for 7 days


OutcomesPrimary: difference in symptom score change at day 7
Secondary: change in individual symptom severity. Patient satisfaction (IMPSS), physician assessment (IMOS). Adverse effects


NotesInterim report was provided for 2008 version of review by the investigator (Schwabe Pharmaceuticals). Full paper published preceding current update. For analysis, this study is divided into 3 parts (1 treatment arm, 1/3 of control numbers and control events). This trial is part of Kamin 2010, representing 1 treatment arm and 1/3 each of the number of control events and the number of controls (see methods)

Kamin 2010b - 20 mg

MethodsDose-finding RCT (second of 3 treatment arms), double-blind, multi-center


ParticipantsChildren (6 to 18 years), acute bronchitis, < 48 hours past onset
Setting: in- and outpatient departments, Ukraine


InterventionsP. sidoides 3 x 20 mg tablets versus placebo for 7 days


OutcomesPrimary: difference in symptom score change at day 7
Secondary: change in individual symptom severity. Patient satisfaction (IMPSS), physician assessment (IMOS). Adverse effects


NotesInterim report was provided for 2008 version of review by the investigator (Schwabe Pharmaceuticals). Full paper published preceding current update. For analysis, this study is divided into 3 parts (1 treatment arm, 1/3 of control numbers and control events). This trial is part of Kamin 2010, representing 1 treatment arm and 1/3 each of the number of control events and the number of controls (see Methods)

Kamin 2010b - 30 mg

MethodsDose-finding RCT (third of 3 treatment arms), double-blind, multi-center


ParticipantsChildren (6 to 18 years), acute bronchitis, < 48 hours past onset
Setting: in- and outpatient departments, Ukraine


InterventionsP. sidoides 3 x 30 mg tablets versus placebo for 7 days


OutcomesPrimary: difference in symptom score change at day 7
Secondary: change in individual symptom severity. Patient satisfaction (IMPSS), physician assessment (IMOS). Adverse effects


NotesInterim report was provided for 2008 version of review by the investigator (Schwabe Pharmaceuticals). Full paper published preceding current update. For analysis, this study is divided into 3 parts (1 treatment arm, 1/3 of control numbers and control events). This trial is part of Kamin 2010, representing 1 treatment arm and 1/3 each of the number of control events and the number of controls (see Methods)

Kamin 2012

MethodsRCT, double-blind, multi-center


Participants220 children (1 to 18 years), acute bronchitis, < 48 hours past onset
Setting: in- and outpatient departments, Ukraine


InterventionsP. sidoides (alcoholic root extract) 3 x 10 to 30 drops (depending on age of child) versus placebo for 7 days


OutcomesPrimary: difference in symptom score change at day 7
Secondary: change in individual symptom severity. Patient satisfaction (IMPSS), physician assessment (IMOS). Adverse effects


NotesInterim report was provided for 2008 version of review by the investigator (Schwabe Pharmaceuticals). Full paper published preceding current update


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random list, balanced block randomization, stratified by age group (p.220)

Allocation concealment (selection bias)Low riskLength of blocks withheld from study centers (p.220)

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble-blinding, integrity of blinding not assessed (p.220)

Incomplete outcome data (attrition bias)
All outcomes
Low riskFlow chart provided (p.221), low attrition (2/111; 2/107), non-differential, ITT analysis

Selective reporting (reporting bias)Unclear riskPrimary outcome reported, additional outcome information provided as requested

Validated outcome assessment
All outcomes
Unclear riskUnvalidated score used for reporting, additional information supplied but assumes BSS = 0 for absence of symptoms

Lizogub 2007

MethodsRCT, double-blind, multi-center


Participants103 adults (18 to 55 years), common cold, 24 to 48 hours past onset
Setting: in- and outpatient departments, practices, Ukraine


InterventionsP. sidoides (alcoholic root extract) 3 x 30 drops versus placebo for 10 days


OutcomesPrimary: sum of symptom severity differences of cold intensity score day 1 to 5
Secondary: complete resolution; change in individual symptom severity. Patient satisfaction (IMPSS), physician assessment (IMOS). Days off work. Adverse effects


NotesMissing data supplied by investigator (2009 version, low dose only). High dose results not published (requested for 2013 version)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomization list (p.575)

Allocation concealment (selection bias)Low riskBlocks of study medication, block size not revealed (p.575)

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble-blinding, integrity of blinding not assessed (p.575, investigator information)

Incomplete outcome data (attrition bias)
All outcomes
Low riskFlow chart provided (p.576), low attrition (1/52; 1/51), non-differential, ITT analysis

Selective reporting (reporting bias)High riskResults for low dose only reported, some additional outcome information provided as requested

Validated outcome assessment
All outcomes
Unclear riskUnvalidated score used for reporting, additional information supplied but assumes BSS = 0 for absence of symptoms

Matthys 2007a

MethodsRCT, double-blind, multi-center


Participants217 adults, acute bronchitis, < 48 hours past onset
Setting: outpatient departments, Russia


InterventionsP. sidoides (alcoholic root extract) 3 x 30 drops versus placebo for 7 days


OutcomesPrimary: difference in symptom score change at day 7
Secondary: change in individual symptom severity. Patient satisfaction (IMPSS), physician assessment (IMOS). Adverse effects


NotesDetails on treatment assignment clarified by investigator; missing data supplied by investigator


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomization schedules were prepared centrally, p.325

Allocation concealment (selection bias)Low riskCentral randomization, p.325 and investigator information

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble-blinding, integrity of blinding not assessed, p.325

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskFlowchart provided, some differential loss to follow-up (withdrawals 6/108 and 13/109), ITT analysis, p.326

Selective reporting (reporting bias)Unclear riskAll main results reported, not all relevant to study question

Validated outcome assessment
All outcomes
Unclear riskUnvalidated score used for reporting, additional information supplied but assumes BSS = 0 for absence of symptoms

Matthys 2010

MethodsDose-finding RCT (3 treatment arms), double-blind, multi-center


Participants399 adults, acute bronchitis, < 48 hours past onset
Setting: in- and outpatient departments, Ukraine


InterventionsP. sidoides 3 x 10/20/30 mg tablets versus placebo for 7 days


OutcomesPrimary: difference in symptom score change at day 7
Secondary: change in individual symptom severity. Patient satisfaction (IMPSS), physician assessment (IMOS). Adverse effects


NotesInterim report was provided for 2008 version of review by the investigator (Schwabe Pharmaceuticals). Full paper published preceding current update. For analysis, this study is divided into 3 parts (1 treatment arm, 1/3 of control numbers and control events)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random list, p.1414

Allocation concealment (selection bias)Low riskCentral randomization, block length withheld, p.1414 and investigator information

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble-blinding, integrity of blinding not assessed, p.1414 and investigator information

Incomplete outcome data (attrition bias)
All outcomes
Low riskFlowchart provided, minimal loss to follow-up (withdrawals 1/102, 2/102, 0/101, 1/101), ITT analysis, p.1416

Selective reporting (reporting bias)Unclear riskAll main results reported, not all relevant to study question

Validated outcome assessment
All outcomes
Unclear riskUnvalidated score used for reporting, additional information supplied but assumes BSS = 0 for absence of symptoms

Matthys 2010 - 10 mg

MethodsDose-finding RCT (first of 3 treatment arms), double-blind, multi-center


ParticipantsAdults, acute bronchitis, < 48 hours past onset
Setting: in- and outpatient departments, Ukraine


InterventionsP. sidoides 3 x 10 mg tablets versus placebo for 7 days


OutcomesPrimary: difference in symptom score change at day 7
Secondary: change in individual symptom severity. Patient satisfaction (IMPSS), physician assessment (IMOS). Adverse effects


NotesInterim report was provided for 2008 version of review by the investigator (Schwabe Pharmaceuticals). Full paper published preceding current update. For analysis, this study is divided into 3 parts (1 treatment arm, 1/3 of control numbers and control events). This trial is part of Matthys 2010, representing 1 treatment arm and 1/3 each of the number of control events and the number of controls (see Methods)

Matthys 2010 - 20 mg

MethodsDose-finding RCT (second of 3 treatment arms), double-blind, multi-center


ParticipantsAdults, acute bronchitis, < 48 hours past onset
Setting: in- and outpatient departments, Ukraine


InterventionsP. sidoides 3 x 20 mg tablets versus placebo for 7 days


OutcomesPrimary: difference in symptom score change at day 7
Secondary: change in individual symptom severity. Patient satisfaction (IMPSS), physician assessment (IMOS). Adverse effects


NotesInterim report was provided for 2008 version of review by the investigator (Schwabe Pharmaceuticals). Full paper published preceding current update. For analysis, this study is divided into 3 parts (1 treatment arm, 1/3 of control numbers and control events). This trial is part of Matthys 2010, representing 1 treatment arm and 1/3 each of the number of control events and the number of controls (see Methods)

Matthys 2010 - 30 mg

MethodsDose-finding RCT (third of 3 treatment arms), double-blind, multi-center


ParticipantsAdults, acute bronchitis, < 48 hours past onset
Setting: in- and outpatient departments, Ukraine


InterventionsP. sidoides 3 x 30 mg tablets versus placebo for 7 days


OutcomesPrimary: difference in symptom score change at day 7
Secondary: change in individual symptom severity. Patient satisfaction (IMPSS), physician assessment (IMOS). Adverse effects


NotesInterim report was provided for 2008 version of review by the investigator (Schwabe Pharmaceuticals). Full paper published preceding current update. For analysis, this study is divided into 3 parts (1 treatment arm, 1/3 of control numbers and control events). This trial is part of Matthys 2010, representing 1 treatment arm and 1/3 each of the number of control events and the number of controls (see Methods)

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Bachert 2005RCT, double -blind, n = 272

Adults with acute maxillary sinusitis

Intervention: P. sidoides (alcoholic root extract), comparator: placebo

Primary outcome: difference in symptoms

Reason for exclusion: insufficient data - data only available in abstract form. According to manufacturer full publication not planned due to flawed design (high drop-out rates). Abstract also includes data from another study for which unpublished data were available

Bereznoj 2009Prospective cohort, open-label, n = 1000

Children and young adults with tonsillitis

Intervention: P. sidoides (alcoholic root extract)

Primary outcome: difference in symptoms

Reason for exclusion: uncontrolled design

Bereznoy 2003RCT, double-blind, n = 144
Children with pharyngotonsillitis (non-streptococcal)

Primary outcome: difference in symptom score
Intervention: P. sidoides (alcoholic root extract), comparator: placebo

Reason for exclusion: high differential drop-out, problematic withdrawal criteria resulting in high risk of bias (attrition bias)

Blochin 1999RCT, open-label, n = 60
Children with acute bronchitis

Intervention: P. sidoides (alcoholic root extract), comparator: acetylcysteine

Primary outcome: difference in symptom score

Reason for exclusion: open-label

Blochin 2000RCT, open-label, n = 60
Children with tonsillopharyngitis

Intervention: P. sidoides (alcoholic root extract), comparator: therapeutic compresses ("Priessnitz Wickel") and gargling with vinegar
Primary outcome: difference in symptom score

Reason for exclusion: open-label

Dome 1996Prospective cohort, open-label, n = 742
Children with acute bronchitis or acute exacerbation of chronic bronchitis
Primary outcome: difference in symptom score
Intervention: P. sidoides (alcoholic root extract)

Reason for exclusion: uncontrolled design

Haidvogl 1996Prospective cohort, open-label, n = 259
Adults with acute bronchitis or acute exacerbation of chronic bronchitis. Duplicate publication - subset of Dome 1996
Primary outcome: difference in symptom score
Intervention: P. sidoides (alcoholic root extract)

Reason for exclusion: uncontrolled design

Koenig 1995Narrative review including imprecise report on original study, obviously observational, n = 641

Children and adults with various respiratory tract infections

Intervention: P. sidoides (alcoholic root extract)

Primary outcome: improvement of symptoms, global assessment (self and physician)

Reason for exclusion: insufficient information, seems uncontrolled design

Luna 2011RCT, double-blind, n = 28

Marathon runners

Primary outcome: difference in symptom score
Intervention: P. sidoides (alcoholic root extract), comparator: placebo

Primary outcome: IgA and cytokine expression

Reason for exclusion: not in respiratory tract infection

Martins Kirk 2007Prospective cohort, open-label, n = 1667

Children and adults with pharyngotonsillitis

Intervention: P. sidoides (alcoholic root extract)

Primary outcome: improvement of symptoms

Reason for exclusion: uncontrolled design

Matthys 2003RCT, double-blind, n = 468
Adults with acute bronchitis

Intervention: P. sidoides (alcoholic root extract), comparator: placebo
Primary outcome: difference in symptom score

Reason for exclusion: high differential drop-out, problematic withdrawal criteria resulting in high risk of bias (attrition bias)

Matthys 2007bProspective cohort, open-label, n = 205
Adults with acute bronchitis or acute exacerbation of chronic bronchitis
Intervention: P. sidoides (alcoholic root extract)

Primary outcome: improvement of symptoms

Reason for exclusion: uncontrolled design

Matthys 2007cProspective cohort, open-label, n = 2099

Children and adults with acute bronchitis

Intervention: P. sidoides (alcoholic root extract)

Primary outcome: improvement of symptoms

Reason for exclusion: uncontrolled design

Matthys 2013RCT, double-blind, n = 200

Adults with COPD or chronic bronchitis

Intervention: P. sidoides (alcoholic root extract), comparator: placebo

Primary outcome: time to acute exacerbation of COPD

Reason for exclusion: underlying chronic disease (COPD)

Patiroglu 2012RCT, double-blind, n = 28

Children with immunodeficiency of infancy

Intervention: P. sidoides (alcoholic root extract), comparator: placebo

Primary outcome: improvement of various cold symptoms

Reason for exclusion: underlying immunodeficiency

Perez 2011Prospective cohort, open-label, n = 305

Mixed group (children and adult, bronchitis, sinusitis or tonsillitis)

Intervention: P. sidoides (alcoholic root extract)

Primary outcome: improvement of symptoms

Reason for exclusion: uncontrolled design

Roots 2004RCT (phase II), open-label, n = 28

Healthy volunteers

Intervention: P. sidoides (alcoholic root extract), comparator: placebo

Primary outcome: pharmacodynamics

Reason for exclusion: not respiratory tract infection

Schapowal 2007Prospective cohort, open-label, not controlled, n = 361

Children and adults with sinusitis (acute and chronic)

Intervention: P. sidoides (alcoholic root extract)

Primary outcome: improvement of score/symptoms

Reason for exclusion: uncontrolled design

Tahan 2013RCT, open-label, n = 61

Children with upper respiratory tract infection and asthma
Intervention: P. sidoides (alcoholic root extract), comparator: placebo

Primary outcome: prevention of asthma attacks during viral infection

Reasons for exclusion: underlying chronic disease, open-label

 
Characteristics of studies awaiting assessment [ordered by study ID]
Bachert 2004

MethodsRCT, double-blind

Participants272 adults with acute maxillary sinusitis

InterventionsP. sidoides alcoholic extract versus placebo

OutcomesNot known yet

NotesPerformed in Ukraine, unpublished material only (investigator supplied)

Beck 2001

MethodsRCT, double-blind

Participants124 children (age 6 to 10) with angina catarrhalis

InterventionsP. sidoides alcoholic extract versus placebo

OutcomesNot known yet

NotesPerformed in Ukraine, unpublished material only (investigator supplied)

Heger 2002

MethodsRCT, double-blind

Participants215 children (age 6 to 12) with acute bronchitis

InterventionsP. sidoides alcoholic extract versus acetylcysteine

OutcomesNot known yet

NotesPerformed in Russia, unpublished material only (investigator supplied)

Heger 2003

MethodsRCT, double-blind, 3 arms (2 treatment, 1 placebo)

Participants637 adults with acute bronchitis

InterventionsP. sidoides alcoholic extract versus placebo

OutcomesNot known yet

NotesPerformed in Germany and Ukraine, unpublished material only (investigator supplied)

ISRCTN86579667

MethodsRCT

Participants78 children with acute non-streptococcal tonsillopharyngitis (6 to 10 years)

InterventionsEPs 7630, 20 drops per hour during the first 1 to 2 days, followed by 20 drops 3 times daily versus placebo

OutcomesNot known

NotesRegistry information only, need to be checked for publication, ISO Arzneimittel GmbH & Co KG (Germany); reported completed, started enrolment in 2003

Wolf 2011

MethodsRCT, double-blind, 3 arms (2 treatment, 1 placebo)

Participants72 adult healthy volunteers

InterventionsP. sidoides alcoholic extract versus placebo

OutcomesNot known yet

NotesPerformed in Germany, unpublished material only (investigator supplied)

 
Characteristics of ongoing studies [ordered by study ID]
EUCTR2007-004923-39-DE

Trial name or titleEfficacy and tolerability of EPs® 7630 film-coated tablets in patients (>=18 years old) with Acute Rhinopharyngitis (ARP)

MethodsRCT, double-blind

ParticipantsAdults with acute rhinopharyngitis, sample/target size not reported

InterventionsEPs® 7630 solution versus placebo

OutcomesArea under the curve (AUC) of the total score of rhinopharyngitis-relevant symptoms (RPS) from baseline (day 1, visit 1) to day 5 (visit 3). Change in total score of rhinopharyngitis-relevant symptoms (RPS), number of patients who experience a reduction in total score of RPS, number of patients with complete remission of RPS, change in individual rhinopharyngitis-relevant symptoms (RPS), patient's ability to work or to attend school/college, sleep quality, health-related quality of life, patient's satisfaction with treatment (IMPSS), consumption of paracetamol tablets, treatment outcome (IMOS)

Starting dateNovember 2007 (first enrolment)

Contact informationNot reported (Schwabe Pharmaceuticals)

NotesPerformed in Bulgaria, status not reported, potential duplicate of EUCTR2007-005579-33-BG

EUCTR2007-005579-33-BG

Trial name or titleEfficacy and tolerability of EPs® 7630 film-coated tablets in patients (>=18 years old) with Acute Rhinopharyngitis (ARP)

MethodsRCT, double-blind

ParticipantsAdults with acute rhinopharyngitis, sample/target size not reported

InterventionsEPs® 7630 solution versus placebo

OutcomesArea under the curve (AUC) of the total score of rhinopharyngitis-relevant symptoms (RPS) from baseline (day 1, visit 1) to day 5 (visit 3). Change in total score of rhinopharyngitis-relevant symptoms (RPS), number of patients who experience a reduction in total score of RPS, number of patients with complete remission of RPS, change in individual rhinopharyngitis-relevant symptoms (RPS), patient's ability to work or to attend school/college, sleep quality, health-related quality of life, patient's satisfaction with treatment (IMPSS), consumption of paracetamol tablets, treatment outcome (IMOS)

Starting dateAugust 2008 (first enrolment)

Contact informationNot reported (Schwabe Pharmaceuticals)

NotesPerformed in Bulgaria, status not reported, potential duplicate of EUCTR2007-004923-39-DE

EUCTR2007-005797-31-BG

Trial name or titleEfficacy and tolerability of EPs® 7630 film-coated tablets in patients (>=18 years old) with Acute Rhinopharyngitis (ARP)

MethodsRCT, double-blind

ParticipantsAdults with acute rhinopharyngitis, sample/target size not reported

InterventionsEPs® 7630 film-coated tablets versus placebo

OutcomesArea under the curve (AUC) of the total score of rhinopharyngitis-relevant symptoms (RPS) from baseline (day 1, visit 1) to day 5 (visit 3). Change in total score of rhinopharyngitis-relevant symptoms (RPS), number of patients who experience a reduction in total score of RPS, number of patients with complete remission of RPS, change in individual rhinopharyngitis-relevant symptoms (RPS), patient's ability to work or to attend school/college, sleep quality, health-related quality of life, patient's satisfaction with treatment (IMPSS), consumption of paracetamol tablets, treatment outcome (IMOS)

Starting dateAugust 2008 (first enrolment)

Contact informationNot reported (Schwabe Pharmaceuticals)

NotesPerformed in Bulgaria, status not reported

EUCTR2011-002652-14-DE

Trial name or titleSafety and tolerability of Pelargonium sidoides extract EPs® 7630 in children (1 to 5 years old) suffering from acute bronchitis: a randomized controlled trial

MethodsRCT, open-label, multi-center

Participants600 (target) children with acute bronchitis (1 to 5 years)

Interventions2.5 ml EPs® 7630 syrup 3 times/day or 10 drops EPs® 7630 solution 3 times/day for 7 consecutive days

OutcomesAdverse events, changes in individual respiratory tract infection symptoms as well as the total symptoms score

Starting date1 October 2011 (first enrolment)

Contact informationFA Malek; Dr. Willmar Schwabe GmbH & Co KG (Germany)

NotesPotential duplicate of ISRCTN77419032

ISRCTN77419032

Trial name or titleSafety and tolerability of Pelargonium sidoides extract EPs® 7630 in children (1 to 5 years old) suffering from acute bronchitis: a randomized controlled trial

MethodsRCT, open-label, multi-center

Participants600 (target) children with acute bronchitis (1 to 5 years)

Interventions2.5 ml EPs® 7630 syrup 3 times/day or 10 drops EPs® 7630 solution 3 times/day for 7 consecutive days

OutcomesAdverse events, changes in individual respiratory tract infection symptoms as well as the total symptoms score

Starting date1 October 2011 (first enrolment)

Contact informationFA Malek; Dr. Willmar Schwabe GmbH & Co KG (Germany)

NotesRegistry information only, reported recruiting, last entry February 2012

JPRN-UMIN000003815

Trial name or titleEfficacy of a Pelargonium sidoides preparation in patients with the upper respiratory infection

MethodsRCT, 2 arms

Participants200 children and adults (target), acute upper respiratory tract infection (cold)

InterventionsP. sidoides alcoholic extract versus placebo (10 days)

OutcomesCold intensity score (CIS), General Well-Being Index

Starting dateJuly 2010 (first enrolment)

Contact informationK Nakayama, University of Tokyo Department of Infectious disease, Japan 

NotesPublic recruitment in Japan, public sponsor; registry information only, reported recruiting, last entry April 2013. Contact person contacted by email 22 May 2013.

NCT01420445

Trial name or titleRandomized, Double-blind, Placebo/Active-controlled, Multi-center, Phase 3 Clinical Trial to Investigate the Safety/Tolerability and Efficacy of YHD001 After Oral Administration in Patients With Acute or Chronic Bronchitis

MethodsRCT, double-blind, 4 arms (2 YHD001, 1 Pelargonium sidoides, 1 placebo)

Participants116 adults with acute bronchitis

InterventionsYHD001 (dose-finding) versus P elargonium sidoides versus placebo

OutcomesChange of total symptom score from baseline to the end of treatment (time frame: 7 days); safety assessment (time frame: 7 days); time to response (time frame: 7 days)

Starting dateSeptember 2011 (first enrolment)

Contact informationYuhan Corporation, Korea

NotesPerformed in Korea, registry information only, reported ongoing (recruitment closed), last entry February 2012. No contact person provided. 2 physicians in the recruitment center approached by email for more information 22 May 2013

 
Comparison 1. P. sidoides versus placebo, acute bronchitis in adults

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Failure to recover by day seven (complete resolution of all symptoms)5Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Liquid preparation
2341Risk Ratio (M-H, Random, 95% CI)0.66 [0.52, 0.83]

    1.2 Tablet preparation
3405Risk Ratio (M-H, Random, 95% CI)0.95 [0.91, 0.99]

 2 Failure to resolve key symptom by day seven: cough5Risk Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Liquid preparation
2341Risk Ratio (M-H, Random, 95% CI)0.63 [0.47, 0.85]

    2.2 Tablet preparation
3405Risk Ratio (M-H, Random, 95% CI)0.94 [0.90, 0.98]

 3 Failure to resolve key symptom by day seven: sputum5746Risk Ratio (M-H, Random, 95% CI)0.70 [0.60, 0.82]

    3.1 Liquid preparation
2341Risk Ratio (M-H, Random, 95% CI)0.65 [0.54, 0.78]

    3.2 Tablet preparation
3405Risk Ratio (M-H, Random, 95% CI)0.73 [0.57, 0.94]

 
Comparison 2. P. sidoides versus placebo, acute bronchitis in children

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Failure to recover by day seven (complete resolution of all symptoms)5Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Liquid preparation
2420Risk Ratio (M-H, Fixed, 95% CI)0.82 [0.77, 0.88]

    1.2 Tablet preparation
3399Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.89, 1.03]

 2 Failure to resolve key symptom by day seven: cough5Risk Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Liquid preparation
2420Risk Ratio (M-H, Random, 95% CI)0.82 [0.76, 0.88]

    2.2 Tablet preparation
3399Risk Ratio (M-H, Random, 95% CI)0.96 [0.86, 1.07]

 3 Failure to resolve key symptom by day seven: sputum5Risk Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Liquid preparation
2272Risk Ratio (M-H, Random, 95% CI)0.55 [0.33, 0.91]

    3.2 Tablet preparation
3399Risk Ratio (M-H, Random, 95% CI)0.87 [0.71, 1.06]

 
Comparison 3. P. sidoides versus placebo, acute sinusitis in adults

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Failure to recover by day 21 (complete resolution of all symptoms)1103Risk Ratio (M-H, Fixed, 95% CI)0.43 [0.30, 0.62]

 2 Failure to resolve key symptom by day 21: nasal discharge1103Risk Ratio (M-H, Fixed, 95% CI)0.21 [0.11, 0.40]

 3 Failure to resolve key symptom by day 21: headache1103Risk Ratio (M-H, Fixed, 95% CI)0.23 [0.12, 0.44]

 
Comparison 4. P. sidoides versus placebo, the common cold in adults

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Failure to recover by day 5 (complete resolution of all symptoms)1103Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.90, 1.03]

 2 Failure to resolve key symptom by day 5: sore throat1103Risk Ratio (M-H, Fixed, 95% CI)0.85 [0.66, 1.11]

 3 Failure to resolve key symptom by day 5: nasal drainage1103Risk Ratio (M-H, Fixed, 95% CI)0.82 [0.72, 0.95]

 4 Failure to resolve key symptom by day 5: nasal congestion1103Risk Ratio (M-H, Fixed, 95% CI)0.82 [0.72, 0.95]

 5 Failure to recover by day 10 (complete resolution of all symptoms)1103Risk Ratio (M-H, Fixed, 95% CI)0.41 [0.29, 0.60]

 6 Failure to resolve key symptom by day 10: sore throat1103Risk Ratio (M-H, Fixed, 95% CI)0.11 [0.01, 1.97]

 7 Failure to resolve key symptom by day 10: nasal drainage1103Risk Ratio (M-H, Fixed, 95% CI)0.18 [0.04, 0.76]

 8 Failure to resolve key symptom by day 10: nasal congestion1103Risk Ratio (M-H, Fixed, 95% CI)0.29 [0.09, 1.01]

 9 Days off work1103Mean Difference (IV, Fixed, 95% CI)-1.30 [-2.06, -0.54]

 
Comparison 5. P. sidoides versus placebo, any indication

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Patients with adverse events81771Risk Ratio (M-H, Fixed, 95% CI)1.32 [1.04, 1.66]

 2 Adverse events leading to withdrawal81771Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.35, 2.27]

 3 Failure to resolve all symptoms at prespecified day - publication bias8Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Summary of findings for the main comparison. P. sidoides for the treatment of acute bronchitis in adults

P. sidoides for the treatment of acute bronchitis in adults

Patient or population: adults with acute bronchitis
Settings: in- and outpatient departments, GP practices; Ukraine and Russia
Intervention: P. sidoides versus placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No. of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlP. sidoides

Failure to recover by day 7 (complete resolution of all symptoms) - liquid preparationStudy populationRR 0.66
(0.52 to 0.83)
341
(2 studies)
⊕⊕⊝⊝
low1,2,3

953 per 1000629 per 1000
(495 to 791)

Moderate

960 per 1000634 per 1000
(499 to 797)

Failure to recover by day 7 (complete resolution of all symptoms) - tablet preparationStudy populationRR 0.95
(0.91 to 0.99)
405
(1 study)
⊕⊕⊝⊝
low1,3,4

990 per 1000941 per 1000
(901 to 980)

Moderate

1000 per 1000950 per 1000
(910 to 990)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1Outcome on request only, investigator-initiated studies only, minor attrition problems, success of blinding not assessed.
2Relevant statistical heterogeneity, not completely solved by subgroup analyses, but both studies and all outcomes clearly in same direction.
3Insufficient number of studies to perform statistical testing, but funnel plot across all conditions strongly suggests small study bias.
41 study only.
 
Summary of findings 2. P. sidoides for treating acute bronchitis in children

P. sidoides for treating acute bronchitis in children

Patient or population: children with acute bronchitis
Settings: in- and outpatient departments, GP practices; Ukraine and Russia
Intervention: P. sidoides versus placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No. of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlP. sidoides

Failure to recover by day 7 (complete resolution of all symptoms) - liquid preparationStudy populationRR 0.82
(0.77 to 0.88)
420
(2 studies)
⊕⊕⊝⊝
low1,2

971 per 1000796 per 1000
(748 to 854)

Moderate

971 per 1000796 per 1000
(748 to 854)

Failure to recover by day 7 (complete resolution of all symptoms) - tablet preparationStudy populationRR 0.96
(0.89 to 1.03)
399
(1 study)
⊕⊕⊝⊝
low1

911 per 1000874 per 1000
(811 to 938)

Moderate

912 per 1000876 per 1000
(812 to 939)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1Outcome on request only, investigator-initiated studies only, minor attrition problems, success of blinding not assessed.
2Insufficient number of studies to perform statistical testing, but funnel plot across all conditions strongly suggests small study bias.
 
Summary of findings 3. P. sidoides versus placebo for treating acute sinusitis in adults

P. sidoides for treating acute sinusitis in adults

Patient or population: adults with acute sinusitis
Settings: in- and outpatient departments, ENT practices; Ukraine
Intervention: P. sidoides versus placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No. of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlP. sidoides

Failure to recover by day 21 (complete resolution of all symptoms)Study populationRR 0.43
(0.3 to 0.62)
103
(1 study)
⊕⊝⊝⊝
very low1,2,3

904 per 1000389 per 1000
(271 to 560)

Moderate

904 per 1000389 per 1000
(271 to 560)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1Outcome on request only, investigator-initiated studies only, minor attrition problems, success of blinding not assessed.
21 small study only, very wide confidence interval.
3Insufficient number of studies to perform statistical testing, but funnel plot across all conditions strongly suggests small study bias.
 
Summary of findings 4. P. sidoides for common cold in adults

P. sidoides for common cold in adults

Patient or population: adults with common cold
Settings: in- and outpatient departments, GP practices; Ukraine
Intervention: P. sidoides versus placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No. of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlP. sidoides

Failure to recover by day 5 (complete resolution of all symptoms)Study populationRR 0.96
(0.9 to 1.03)
103
(1 study)
⊕⊝⊝⊝
very low1,2,3

1000 per 1000960 per 1000
(900 to 1000)

Moderate

1000 per 1000960 per 1000
(900 to 1000)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1Outcome on request only, investigator-initiated studies only, minor attrition problems, success of blinding not assessed.
21 small study only.
3Insufficient number of studies to perform statistical testing, but funnel plot across all conditions strongly suggests small study bias.