Influence of EPs 7630 on Antipyretic Comedication and Recovery from Acute Tonsillopharyngitis in Children: A Meta-analysis of Randomized, Placebo-Controlled, Clinical Trials

Georg Seifert; Petra Funk; Thorsten Reineke; Walter Lehmacher

doi:10.1055/s-0040-1722205

Journal of Pediatric Infectious Diseases, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · J Pediatr Infect Dis 2021; 16(03): 122-128
DOI: 10.1055/s-0040-1722205

Original Article

Influence of EPs 7630 on Antipyretic Comedication and Recovery from Acute Tonsillopharyngitis in Children: A Meta-analysis of Randomized, Placebo-Controlled, Clinical Trials

Autoren

Georg Seifert

¹Department of Paediatric Oncology/Haematology, Otto-Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité–Universitätsmedizin Berlin, Berlin, Germany

²Department of Pediatrics, Faculty of Medicine, University of São Paulo, São Paulo, Brazil
Petra Funk

³Department of Clinical Research, Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany
Thorsten Reineke

³Department of Clinical Research, Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany
Walter Lehmacher

⁴Institute for Medical Statistics, Unit of Informatics and Epidemiology, University of Cologne, Cologne, Germany

Abstract

Objective Acute tonsillopharyngitis (ATP) is a common, seasonal infection of predominantly viral origin. Management is aimed at shortening the course of the disease and restoring the comfort of the patient. We performed a meta-analysis to investigate whether treatment with the Pelargonium sidoides extract EPs 7630 reduces the use of antipyretic comedication (i.e., acetaminophen) in children suffering from ATP.

Methods Studies were identified from clinical trial registries and medical literature. Randomized, placebo-controlled, clinical trials investigating EPs 7630 in children with ATP and reporting the coadministration of paracetamol were eligible. Based on the raw data of eligible trials, we analyzed cumulative paracetamol use, as well as the ability to attend school at the end of treatment. Three trials including a total of 345 children aged 6 to 10 years and suffering from non-β-hemolytic streptococcal ATP were identified and eligible. Children were administered EPs 7630 or placebo for 6 days.

Results Compared with placebo, EPs 7630 reduced the cumulative paracetamol dose by an average of 449 mg (95% confidence interval [CI]: 252–646 mg; p < 0.001). A total of 19.1% (EPs 7630) and 71.5% (placebo) of children were still unable to attend school at the end of the treatment (risk ratio = 0.28; 95% CI: 0.16–0.48; p < 0.001).

Conclusion Our meta-analysis demonstrates that EPs 7630 reduced the use of antipyretic comedication and accelerated recovery.

Keywords

acute tonsillopharyngitis - children - meta-analysis - paracetamol - Pelargonium sidoides

Volltext

Referenzen

References
1 Shaikh N, Leonard E, Martin JM. Prevalence of streptococcal pharyngitis and streptococcal carriage in children: a meta-analysis. Pediatrics 2010; 126 (03) e557-e564
2 Regoli M, Chiappini E, Bonsignori F, Galli L, de Martino M. Update on the management of acute pharyngitis in children. Ital J Pediatr 2011; 37: 10
3 Bisno AL. Acute pharyngitis. N Engl J Med 2001; 344 (03) 205-211
4 Proenca-Modena JL, Pereira Valera FC, Jacob MG. et al. High rates of detection of respiratory viruses in tonsillar tissues from children with chronic adenotonsillar disease. PLoS One 2012; 7 (08) e42136
5 Stelter K. Tonsillitis and sore throat in children. GMS Curr Top Otorhinolaryngol Head Neck Surg 2014; 13: Doc07-Doc07
6 McIsaac WJ, Kellner JD, Aufricht P, Vanjaka A, Low DE. Empirical validation of guidelines for the management of pharyngitis in children and adults. JAMA 2004; 291 (13) 1587-1595
7 Chiappini E, Regoli M, Bonsignori F. et al. Analysis of different recommendations from international guidelines for the management of acute pharyngitis in adults and children. Clin Ther 2011; 33 (01) 48-58
8 Section on Clinical Pharmacology and Therapeutics, Committee on Drugs. Sullivan JE, Farrar HC. Fever and antipyretic use in children. Pediatrics 2011; 127 (03) 580-587
9 Cannon JG. Perspective on fever: the basic science and conventional medicine. Complement Ther Med 2013; 21 (Suppl. 01) S54-S60
10 Carey JV. Literature review: should antipyretic therapies routinely be administered to patients with [corrected] fever?. J Clin Nurs 2010; 19 (17–18): 2377-2393
11 Evans SS, Repasky EA, Fisher DT. Fever and the thermal regulation of immunity: the immune system feels the heat. Nat Rev Immunol 2015; 15 (06) 335-349
12 Kluger MJ, Kozak W, Conn CA, Leon LR, Soszynski D. The adaptive value of fever. Infect Dis Clin North Am 1996; 10 (01) 1-20
13 Aminoshariae A, Khan A. Acetaminophen: old drug, new issues. J Endod 2015; 41 (05) 588-593
14 Beasley R, Clayton T, Crane J. et al; ISAAC Phase Three Study Group. Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6-7 years: analysis from phase three of the ISAAC programme. Lancet 2008; 372 (9643): 1039-1048
15 Schillie SF, Shehab N, Thomas KE, Budnitz DS. Medication overdoses leading to emergency department visits among children. Am J Prev Med 2009; 37 (03) 181-187
16 Kayser O, Kolodziej H, Kiderlen AF. Immunomodulatory principles of Pelargonium sidoides . Phytother Res 2001; 15 (02) 122-126
17 Kolodziej H. Fascinating metabolic pools of Pelargonium sidoides and Pelargonium reniforme, traditional and phytomedicinal sources of the herbal medicine Umckaloabo^® . Phytomedicine 2007; 14 (Suppl. 01) 9-17
18 Kolodziej H, Kayser O, Radtke OA, Kiderlen AF, Koch E. Pharmacological profile of extracts of Pelargonium sidoides and their constituents. Phytomedicine 2003; 10 (Suppl. 04) 18-24
19 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. 01) 18-26
20 Michaelis M, Doerr HW, Cinatl Jr J. Investigation of the influence of EPs^® 7630, a herbal drug preparation from Pelargonium sidoides, on replication of a broad panel of respiratory viruses. Phytomedicine 2011; 18 (05) 384-386
21 Theisen LL, Muller CP. EPs^® 7630 (Umckaloabo^®), an extract from Pelargonium sidoides roots, exerts anti-influenza virus activity in vitro and in vivo. Antiviral Res 2012; 94 (02) 147-156
22 Careddu D, Pettenazzo A. Pelargonium sidoides extract EPs 7630: a review of its clinical efficacy and safety for treating acute respiratory tract infections in children. Int J Gen Med 2018; 11: 91-98
23 Agbabiaka TB, Guo R, Ernst E. Pelargonium sidoides for acute bronchitis: a systematic review and meta-analysis. Phytomedicine 2008; 15 (05) 378-385
24 Agbabiaka TB, Guo R, Ernst E. Erratum to “Pelargonium sidoides for acute bronchitis: a systematic review and meta-analysis” [Phytomedicine 15 (2008) 378–385]. Phytomedicine 2009; 16: 798-799
25 Matthys H, Malek FA, Kamin W. EPs^® 7630 in acute respiratory tract infections – a systematic review and meta-analysis of randomised clinical trials. Forsch Komplement Med 2014; 21: 57-58
26 Timmer A, Günther J, Motschall E, Rücker G, Antes G, Kern WV. Pelargonium sidoides extract for treating acute respiratory tract infections. Cochrane Database Syst Rev 2013; 10 (10) CD006323
27 Ulbricht C, Abrams TR, Conquer J. et al. An evidence-based systematic review of umckaloabo (Pelargonium sidoides) by the Natural Standard Research Collaboration. J Diet Suppl 2010; 7 (03) 283-302
28 Matthys H, Lehmacher W, Zimmermann A, Brandes J, Kamin W. EPs 7630 in acute respiratory tract infections – a systematic review and meta-analysis of randomized clinical trials. J Lung Pulm Respir Res 2016; 3: 00068
29 Kamin W, Funk P, Seifert G, Zimmermann A, Lehmacher W. EPs 7630 is effective and safe in children under 6 years with acute respiratory tract infections: clinical studies revisited. Curr Med Res Opin 2018; 34 (03) 475-485
30 Schapowal A, Dobos G, Cramer H. et al. Treatment of signs and symptoms of the common cold using EPs 7630 - results of a meta-analysis. Heliyon 2019; 5 (11) e02904
31 Matthys H, Köhler S, Kamin W. Safety and tolerability of EPs 7630 in clinical trials. Adv Pharmacoepidemiol Drug Saf 2013; 2: 142
32 Cochrane Centre. Review Manager (RevMan) Version 5.2. Accessed December 7, 2020 at: https://training.cochrane.org/online-learning/core-software-cochrane-reviews/revman
33 Lizogub VG, Riley DS, Heger M. Efficacy of a Pelargonium sidoides preparation in patients with the common cold: a randomized, double blind, placebo-controlled clinical trial. Explore (NY) 2007; 3 (06) 573-584
34 Matthys H, Eisebitt R, Seith B, Heger M. Efficacy and safety of an extract of Pelargonium sidoides (EPs 7630) in adults with acute bronchitis. A randomised, double-blind, placebo-controlled trial. Phytomedicine 2003; 10 (Suppl. 04) 7-17
35 Matthys H, Funk P. EPs 7630 improves acute bronchitic symptoms and shortens time to remission. Results of a randomised, double-blind, placebo-controlled, multicentre trial. Planta Med 2008; 74 (06) 686-692
36 Matthys H, Köhler S. Safety and tolerability of EPs^® 7630 (Umckaloabo^®), Planta Med. 2010 ; Abstract SL-29. Doi: 10.1055/s-0030-126426776
37 EH. Das Übel mit der Wurzel packen - Zulu-Medizin bessert Husten, Halsweh und Schnupfen. MMW Fortschr Med 2003; 145 (49) 56
38 Bereznoy VV, Riley DS, Wassmer G, Heger M. Efficacy of extract of Pelargonium sidoides in children with acute non-group A beta-hemolytic streptococcus tonsillopharyngitis: a randomized, double-blind, placebo-controlled trial. Altern Ther Health Med 2003; 9 (05) 68-79
39 Timen G, Zabolotnyi D, Heger M, Lehmacher W. EPs 7630 is effective in children with acute, non-β-haemolytic streptococcal tonsillopharyngitis - Results of a double-blind, placebo-controlled, multicentre trial. Malays J Paediatr Child Health 2015; 21: 36-50
40 Berezhnoi VV, Heger M, Lehmacher W, Seifert G. Clinical efficacy and safety of liquid Pelargonium sidoides preparation (EPs 7630) in children with acute non-streptococcal tonsillopharyngitis. J Compr Pediatr. 2016; 7: e42158
41 Higgins JPT, Green S. eds. Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0. (updated March 2011). Accessed December 7, 2020 at www.handbook.cochrane.org
42 Steele RW. Pharyngitis and tonsillitis. In: McInerny TK, Adam HM, Campbell DE, DeWitt TG, Foy JM, Kamat DM. eds. American Academy of Pediatrics Textbook of Pediatric Care. Elk Grove Village, IL: American Academy of Pediatrics; 2008
43 Seifert G, Brandes-Schramm J, Zimmermann A, Lehmacher W, Kamin W. Faster recovery and reduced paracetamol use - a meta-analysis of EPs 7630 in children with acute respiratory tract infections. BMC Pediatr 2019; 19 (01) 119
44 Conrad A, Jung I, Tioua D. et al. Extract of Pelargonium sidoides (EPs^® 7630) inhibits the interactions of group A-streptococci and host epithelia in vitro. Phytomedicine 2007; 14 (Suppl. 01) 52-59
45 Janecki A, Conrad A, Engels I, Frank U, Kolodziej H. Evaluation of an aqueous-ethanolic extract from Pelargonium sidoides (EPs^® 7630) for its activity against group A-streptococci adhesion to human HEp-2 epithelial cells. J Ethnopharmacol 2011; 133 (01) 147-152
46 Janecki A, Kolodziej H. Anti-adhesive activities of flavan-3-ols and proanthocyanidins in the interaction of group A-streptococci and human epithelial cells. Molecules 2010; 15 (10) 7139-7152
47 Nöldner M, Schötz K. Inhibition of lipopolysaccharid-induced sickness behavior by a dry extract from the roots of Pelargonium sidoides (EPs 7630) in mice. Phytomedicine 2007; 14 (Suppl. 01) 27-31