pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2007-0-6-49-55pulmo-2002Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESЛечение острого бронхита у взрослых экстрактом пеларгонии сидовидной (Pelargonium Sidoides; EPs 7630): рандомизированное двойное слепое плацебо-контролируемое исследованиеTreatment of acute bronchitis in adults with extract of Pelargonium Sidoides: a randomised, double-blind, placebo controlled trialЧучалинА. Г.ChuchalinA. G.

Москва

БерманБ.BermanB.

г. Колледж-Парк, шт. Мэриленд

ЛемахерВ.LemakherV.

г. Кельн

ФГУ НИИ пульмонологии РосздраваRussian FederationУниверситет МэрилендаUnited StatesИнститут медицинской статистики, информатики и эпидемиологии Кельнского университетаGermany200728122007064955Copyright © Чучалин А.Г., Берман Б., Лемахер В., 20072007Чучалин А.Г., Берман Б., Лемахер В.Chuchalin A.G., Berman B., Lemakher V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/2002

Острый бронхит является широко распространенным заболеванием, и, хотя он главным образом вызывается вирусами, для его лечения все еще излишне часто назначаются антибиотики. Поэтому крайне важно оценить применение альтернативного лечения острого бронхита. Цель исследования – оценить эффективность и безопасность препарата пеларгонии сидовидной (EPs 7630 является зарегистрированной торговой маркой компании Dr. Willmar Schwabe, г. Карлсруэ, Германия) по сравнению с плацебо у пациентов с острым бронхитом. В 6 поликлиниках было проведено рандомизированное двойное слепое плацебо-контролируемое исследование с использованием дизайна с плановым промежуточным анализом. В нем участвовали 124 взрослых пациента с диагнозом острого бронхита, началом заболевания ≤ 48 ч, тяжестью симптомов по шкале оценки тяжести симптомов бронхита (BSS) ≥ 5 баллов; все они подписали информированное согласие. Больные принимали EPs 7630 или плацебо (30 капель 3 раза в день) в течение 7 дней. Первичным критерием являлось изменение показателя BSS на 7-й день. Снижение показателя BSS в сравнении с группой контроля на 7-й день составило 7,2 ± 3,1 балла в группе EPs 7630 (n = 64) и 4,9 ± 2,7 балла в группе плацебо (n = 60). Был рассчитан (1,21; 3,56) 95%-ный доверительный интервал различия эффектов между двумя группами лечения (EPs 7630 – плацебо), показывающий значительное улучшение в группе EPs 7630 по сравнению с плацебо на 7-й день (p < 0,0001). Для каждого из 5 индивидуальных симптомов показатели полного выздоровления были значительно выше в группе EPs 7630. В течение первых 4 дней терапевтический эффект был признан у 68,8 % пациентов в группе EPs 7630 по сравнению с 33,3 % пациентов в группе плацебо (p < 0,0001). Качество жизни значительно улучшилось у больных в группе EPs 7630 по сравнению с группой плацебо. Побочные явления наблюдались у 25 из 124 пациентов (EPs 7630 – 15 из 64 пациентов, плацебо – 10 из 60 пациентов). Все побочные явления были оценены как несерьезные. Эффективность препарата EPs 7630 превосходила таковую плацебо в лечении острого бронхита у взрослых. Поэтому может быть предложена эффективная альтернатива для лечения острого бронхита, если нет четких показаний для применения антибиотиков.

Acute bronchitis is a wide-spread disease. Although it is generally caused by viruses, antibiotics are used for its treatment too much often. So it is very important to evaluate alternative therapy of acute bronchitis. The aim of the trial was to assess efficacy and safety of Pelargonium Sidoides (EPs 7630 is a registered trademark of Dr. Willmar Schwabe GmbH & Co, Karlsruhe, Germany) compared to placebo in patients with acute bronchitis. Study design: randomised, double-blind, placebo controlled trial with planned interim analysis. The trial centres: 6 outpatient medical centres. Patients: 124 adult patients with acute bronchitis, onset of the disease ≤ 48 h, and severity of symptoms ≥ 5 according to BSS scale gave written informed concert. EPs 7630 or placebo were administered in the dose of 30 drops t.i.d. during 7 days. The primary outcome measure was BSS scoring at the 7th day of the treatment. BSS scoring decreased by 7.2 ± 3.1 in the EPs 7630 group (n = 64) vs 4.9 ± 2.7 in the placebo group (n = 60). 95 % confidence interval (CI, 1.21, 3.56) for difference of the effects between two groups demonstrated significant improvement in the EPs 7630 in 7 days of the treatment compared to the placebo group (p < 0.0001). The EPs 7630 patients had parameters of complete recovery for every of 5 individual symptoms reliably higher compared to placebo patients. During the first 4 days of the treatment therapeutic effect was noted in 68.8 % of the EPs 7630 group vs 33.3 % of the placebo group (p < 0.0001). Health-related quality of life improved better in the EPs 7630 patients compared to the placebo group. Adverse events were found in 25 of 124 patients: 15 / 64 in the EPs 7630 group and 10 / 60 in the placebo group. All the adverse events were considered as non-serious. The efficacy of EPs 7630 in treatment of adults with acute bronchitis was higher compared to placebo. It could be an efficient alternative drug in therapy of acute bronchitis at the absence of indications for antibiotics administration.

ReferencesBadura B., Lizsch M., Vetter C. Fehlzeiten-Report. Berlin: Springer; 2000.Badura B., Lizsch M., Vetter C. Fehlzeiten-Report. Berlin: Springer; 2000.Gonzales R., Sande M.A. Uncomplicated acute bronchitis. Ann. Intern. Med. 2000; 133: 981–991.Gonzales R., Sande M.A. Uncomplicated acute bronchitis. Ann. Intern. Med. 2000; 133: 981–991.Altiner A., Abholz H.H. Akute Bronchitis und Antibiotika: Hinter-griinde fureine rationale Therapie. Z. Allg. Med. 2001; 77: 358–362.Altiner A., Abholz H.H. Akute Bronchitis und Antibiotika: Hinter-griinde fureine rationale Therapie. Z. Allg. Med. 2001; 77: 358–362.Fahey T., Howie J. Re-evaluation of a randomized controlled trial of antibiotics for minor respiratory illness in general practice. Fam. Pract. 2001; 18: 246–248.Fahey T., Howie J. Re-evaluation of a randomized controlled trial of antibiotics for minor respiratory illness in general practice. Fam. Pract. 2001; 18: 246–248.Murray S., Del Mar C., O'Rourke P. Predictors of an antibiotic prescription by GPs for respiratory tract infections: a pilot. Fam. Pract. 2000; 17: 386–388.Murray S., Del Mar C., O'Rourke P. Predictors of an antibiotic prescription by GPs for respiratory tract infections: a pilot. Fam. Pract. 2000; 17: 386–388.Bent B., Saint S., Vittinghoff E., Grady D. Antibiotics in acute bronchitis: a metaanalysis. Am. J. Med. 1999; 107: 62–67.Bent B., Saint S., Vittinghoff E., Grady D. Antibiotics in acute bronchitis: a metaanalysis. Am. J. Med. 1999; 107: 62–67.Smucny J., Fahey T., Becker L. et al. Antibiotics for acute bronchitis. Cochrane Database Syst. Rev. 2000; 4: CD000245.Smucny J., Fahey T., Becker L. et al. Antibiotics for acute bronchitis. Cochrane Database Syst. Rev. 2000; 4: CD000245.Knutson D., Braun C. Diagnosis and management of acute bronchitis. Am. Fam. Physician. 2002; 65: 2039–2044.Knutson D., Braun C. Diagnosis and management of acute bronchitis. Am. Fam. Physician. 2002; 65: 2039–2044.Kayser O., Kolodziej H. Antibacterial activity of extracts and constituents of Pelargonium sidoides and Pelargonium reniforme. Planta Med. 1997; 63: 508–510.Kayser O., Kolodziej H. Antibacterial activity of extracts and constituents of Pelargonium sidoides and Pelargonium reniforme. Planta Med. 1997; 63: 508–510.Kayser O., Kolodziej H., Kiderlen A.F. Immunomodulatory principles of Pelargonium sidoides. Phytother. Res. 2001; 15: 122–126.Kayser O., Kolodziej H., Kiderlen A.F. Immunomodulatory principles of Pelargonium sidoides. Phytother. Res. 2001; 15: 122–126.Kolodziej H., Kayser O., Radtke O.A. et al. Pharmacological profile of extracts of Pelargonium sidoides and their constituents. Phytomedicine 2003; 10: 18–24.Kolodziej H., Kayser O., Radtke O.A. et al. Pharmacological profile of extracts of Pelargonium sidoides and their constituents. Phytomedicine 2003; 10: 18–24.Haidvogl M., Schuster R., Heger M. Akute Bronchitis im Kindesalter-Multizenter-Studie zut Wirksamkeit und Vertraglichkeit des Phytotherapeutikums Umckaloabo. Z. Phytother. 1996; 17: 300–313.Haidvogl M., Schuster R., Heger M. Akute Bronchitis im Kindesalter-Multizenter-Studie zut Wirksamkeit und Vertraglichkeit des Phytotherapeutikums Umckaloabo. Z. Phytother. 1996; 17: 300–313.Heil C., Reitermann U. Atemwegsand HNO-Infektionen. Therapeutische Erfahrungen mit dem Phylathcrapeurikum Umckaloabo®. Therapiewoche Padiatrec. 1994; 43: 412–415.Heil C., Reitermann U. Atemwegsand HNO-Infektionen. Therapeutische Erfahrungen mit dem Phylathcrapeurikum Umckaloabo®. Therapiewoche Padiatrec. 1994; 43: 412–415.Blochin B., Haidvogl M., Heger M. Umckaloabo im Vergleich zu Acefylcystein bei Kindern mit akuter Bronchitis. Kassenаrzt. 1999; 49: 46–50.Blochin B., Haidvogl M., Heger M. Umckaloabo im Vergleich zu Acefylcystein bei Kindern mit akuter Bronchitis. Kassenаrzt. 1999; 49: 46–50.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, placebocontrolled trial. Phytomedicine 2003; 10 (suppl. IV): 7–17.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, placebocontrolled trial. Phytomedicine 2003; 10 (suppl. IV): 7–17.World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. J. A. M. A. 1997; 277: 925–926.World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. J. A. M. A. 1997; 277: 925–926.European Agency for the Evaluation of Medicinal Product! (HMEA). ICH Topic E 6. Guideline for Good Clinical Practice. Note lot Guidance on Good Clinical Practice (СРМР/IСН/135/95); 1997.European Agency for the Evaluation of Medicinal Product! (HMEA). ICH Topic E 6. Guideline for Good Clinical Practice. Note lot Guidance on Good Clinical Practice (СРМР/IСН/135/95); 1997.Snow V., Mottur2Pilson C., Gonzales R. Principles of appropriate antibiotic use for treatment of acute bronchitis in adults. Ann. Intеrn. Med. 2001: 134: 518–520.Snow V., Mottur2Pilson C., Gonzales R. Principles of appropriate antibiotic use for treatment of acute bronchitis in adults. Ann. Intеrn. Med. 2001: 134: 518–520.Lehmacher W., Wassmer G. Adaptive sample size calculations in group sequential trials. Biometrics 1999; 55: 1286–1290.Lehmacher W., Wassmer G. Adaptive sample size calculations in group sequential trials. Biometrics 1999; 55: 1286–1290.Wassmer G. Statistische Testverfahren fur gruppensequentellei und adaptive Plane in klinischen Studien. Theoretische Konzepte und deren praktische Umsetzung mit SAS. Koln: Alexander Monch; 1999.Wassmer G. Statistische Testverfahren fur gruppensequentellei und adaptive Plane in klinischen Studien. Theoretische Konzepte und deren praktische Umsetzung mit SAS. Koln: Alexander Monch; 1999.Wassmer G., Eisebitt R., Coburger S. Flexible interim analyses in clinical trials using multistage adaptive test designs. Drug Inform. J. 2001; 35: 1131–1146.Wassmer G., Eisebitt R., Coburger S. Flexible interim analyses in clinical trials using multistage adaptive test designs. Drug Inform. J. 2001; 35: 1131–1146.Ware J.E. Jr., Kosinski M., Keller S.D. A 12-item short-form health survey. Construction of scales and preliminary tests of reliability and validity. Med. Care 1996; 34: 220–233.Ware J.E. Jr., Kosinski M., Keller S.D. A 12-item short-form health survey. Construction of scales and preliminary tests of reliability and validity. Med. Care 1996; 34: 220–233.Brooks R. EuroQol: the current state of play. Hlth. Policy 1996; 37: 53–72.Brooks R. EuroQol: the current state of play. Hlth. Policy 1996; 37: 53–72.Johnson J.A., Coons S.J. Comparison of the EQ-5D and SF12 in an adult US sample. Qual. Life Res. 1998; 7: 115–120.Johnson J.A., Coons S.J. Comparison of the EQ-5D and SF12 in an adult US sample. Qual. Life Res. 1998; 7: 115–120.Johnson J.A., Coons S.J., Ergo A., Szava2Kovats G. Valuation of EuroQOL (EQ-5D) health states in an adult US.sample. Pharmacoeconomics 1998; 13: 421–433.Johnson J.A., Coons S.J., Ergo A., Szava2Kovats G. Valuation of EuroQOL (EQ-5D) health states in an adult US.sample. Pharmacoeconomics 1998; 13: 421–433.Kind P., Dolan P., Gudes C., Williams A. Variations in population health status: results from a United Kingdom national questionnaire survey. Br. Med. J. 1998; 316: 736–741.Kind P., Dolan P., Gudes C., Williams A. Variations in population health status: results from a United Kingdom national questionnaire survey. Br. Med. J. 1998; 316: 736–741.Kind P. Measuring quality of life in evaluating clinical interventions: an overview. Ann. Med. 2001; 33: 323–327.Kind P. Measuring quality of life in evaluating clinical interventions: an overview. Ann. Med. 2001; 33: 323–327.European Agency for the Evaluation of Medicinal Products (EMEA). Note for guidance on good clinical practice. ICH-guidelines (human)-efficacy-topic E9. Step 4 note for guidance on statistical principles for clinical trials. СРMP/IСН/363/96 (adopted March 1998).European Agency for the Evaluation of Medicinal Products (EMEA). Note for guidance on good clinical practice. ICH-guidelines (human)-efficacy-topic E9. Step 4 note for guidance on statistical principles for clinical trials. СРMP/IСН/363/96 (adopted March 1998).Pocock S.J. Group sequential methods in the design and analysis of clinical trials. Biometrika 1977; 64:191–199.Pocock S.J. Group sequential methods in the design and analysis of clinical trials. Biometrika 1977; 64:191–199.Gonzales R., Bartlett J.G., Besser R.E. et al. Principles of appropriate antibiotic use for treatment of uncomplicated acute bronchitis: background. Ann. Emerg. Med. 2001; 37: 720–727.Gonzales R., Bartlett J.G., Besser R.E. et al. Principles of appropriate antibiotic use for treatment of uncomplicated acute bronchitis: background. Ann. Emerg. Med. 2001; 37: 720–727.Williamson H.A. A randomised, controlled trial of doxycycline in the treatment of acute bronchitis. J. Fam. Pract. 1984; 19: 481–486.Williamson H.A. A randomised, controlled trial of doxycycline in the treatment of acute bronchitis. J. Fam. Pract. 1984; 19: 481–486.Leophonle P., Murris2Espin M., Berthier A., Dayan M. The place of antimicrobial chemotherapy in the treatment of adults with acute bronchitis: a double-blind placebo-controlled trial. Clin. Microbiol. Infect. 1998; 4: 436–441.Leophonle P., Murris2Espin M., Berthier A., Dayan M. The place of antimicrobial chemotherapy in the treatment of adults with acute bronchitis: a double-blind placebo-controlled trial. Clin. Microbiol. Infect. 1998; 4: 436–441.Evans A.T., Husain S., Durairaj L. et al. Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial. Lancet 2002; 359: 1648–1654.Evans A.T., Husain S., Durairaj L. et al. Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial. Lancet 2002; 359: 1648–1654.Hueston W.J.H., Mainous A.G. III. Acute bronchitis. Am. Font Physician. 1998; 57: 1270–1276.Hueston W.J.H., Mainous A.G. III. Acute bronchitis. Am. Font Physician. 1998; 57: 1270–1276.Kolodziej H., Schulz V. Umckaloabo-Von der traditionellen Anwendung zum modernen Phytotherapeutikum. Dtsch. Apoth.-Ztg. 2003; 143: 55–64.Kolodziej H., Schulz V. Umckaloabo-Von der traditionellen Anwendung zum modernen Phytotherapeutikum. Dtsch. Apoth.-Ztg. 2003; 143: 55–64.Fahey T., Stocks N., Thomas T. Quantitative systematic review of randomised controlled trials comparing antibiotic with placebo for acute cough in adults. Br. Med. J. 1998; 316: 906–910.Fahey T., Stocks N., Thomas T. Quantitative systematic review of randomised controlled trials comparing antibiotic with placebo for acute cough in adults. Br. Med. J. 1998; 316: 906–910.Hirschmann J.V. Antibiotics for common respiratory tract infections in adults. Arch. Intern. Med. 2002; 162: 256–264.Hirschmann J.V. Antibiotics for common respiratory tract infections in adults. Arch. Intern. Med. 2002; 162: 256–264.Hall K.K., Philbrick J., Nadkarni M. Evaluation and treatment of acute bronchitis at an academic teaching clinic. Am. J. Med. Sci. 2003; 325: 7–9.Hall K.K., Philbrick J., Nadkarni M. Evaluation and treatment of acute bronchitis at an academic teaching clinic. Am. J. Med. Sci. 2003; 325: 7–9.

The authors declare that there are no conflicts of interest present.