Clinical efficacy and safety of Ergoferon in flu and other acute respiratory viral infections: a critical evaluation from the standpoint of evidence-based medicine

Abstract

The review presents the results of a critical evaluation of the efficacy and safety of Ergoferon in flu and other acute respiratory viral infections (ARVI) from the standpoint of evidence-based medicine. Data of 6 registered randomized clinical trials (RCTs) can be found in an open source database (grls.ru). The statistical analysis of these RCTs was carried out, which included a pooled estimate of mean values, standard deviations, Student t-test in Welch modification, Fisher's exact test and the risk of bias. All RCTs are prospective, parallel-group, with technically correct randomization: 4 RCTs are with double-blind placebo control, 2 RCTs are open-label (compared with oseltamivir). 715 people took Ergoferon, 172 patients took oseltamivir and 554 patients took placebo. The analyzed criteria included: average duration of fever (reaching body temperature ≤37.2 °C); severity of ARVI symptoms according to the area under the curve"(AUC); proportion of patients with worsening of the disease (development of complications requiring antibiotics or hospitalization); proportion of patients with at least one adverse event. The design, methodology, quality of presentation of the results of RCTs meets modern ethical requirements and standards. The clinical efficacy and safety of Ergoferon for treatment ARVI and flu in adults and children from 6 months were proved in RCTs, among which 4 RCTs have the highest level of evidence - RCTs with double-blind placebo control.

Keywords:flu, evidence-based medicine, treatment, acute respiratory viral infections, randomized clinical trials, Ergoferon

For citation: Nikiforov V.V., Ruzhentsova T.A. Clinical efficacy and safety of Ergoferon in flu and other acute respiratory viral infections: a critical evaluation from the standpoint of evidence-based medicine. Infektsionnye bolezni: novosti, mneniya, obuchenie [Infectious Diseases: News, Opinions, Training]. 2019; 8 (4): 84-97. doi: 10.24411/2305-3496-2019-14011 (in Russian)

References

1. Fashner J., Ericson K., Werner S. Treatment of the common cold in children and adults. Am Fam Physician. 2012; 86 (2): 153-9.

2. van Driel M.L., Scheire S., Deckx L., Gevaert P., De Sutter A. What treatments are effective for common cold in adults and children? BMJ. 2018; 363: k3786.

3. State report "About the state of sanitary and epidemiological welfare of the population in the Russian Federation in 2018". (access 10 October 2019) (in Russian) URL: https://rospotrebnadzor.ru/upload/iblock/798/gosudarstvennyy-doklad-o-sostoyanii-sanitarno_epidemiologicheskogo-blagopoluchiya-naseleniya-v-rossiyskoy-federatsii-v-2018-godu.pdf

4. Rolfes M.A., Foppa I.M., Garg S., Flannery B., et al. Annual estimates of the burden of seasonal influenza in the United States: A tool for strengthening influenza surveillance and preparedness. Influenza Other Respir Viruses. 2018; 12 (1): 132-7.

5. Scholz S., Damm O., Schneider U., Ultsch B., et al. Epidemiology and cost of seasonal influenza in Germany - a claims data analysis. BMC Public Health. 2019; 19 (1): 1090.

6. Principi N., Camilloni B., Alunno A., Polinori I., et al. Drugs for influenza treatment: is there significant news? Front Med (Lausanne). 2019; 6: 109.

7. Uyeki T.M., Bernstein H.H., Bradley J.S. Clinical practice guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza. Clin Infect Dis. 2019; 68 (6): e1-47.

8. Iuliano A.D., Roguski K.M., Chang H.H. Global seasonal influenza-associated mortality collaborator network. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet. 2018; 391: 1285-300.

9. Kalyuzhin O.V. Acute respiratory viral infections: modern challenges, antiviral response, immunoprophylaxis and immunotherapy. Moscow: Medical Information Agency, 2014. (in Russian)

10. Thomsen S.F. Exploring the origins of asthma: Lessons from twin studies. Eur Clin Respir J. 2014; 1 (Suppl 1): URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629771/

doi: 10.3402/ecrj.V1.25535

11. Reddehase M.J. Adverse immunological imprinting by cytomegalovirus sensitizing for allergic airway disease. Med Microbiol Immunol. 2019; 208: 469.

12. Allan G.M., Arroll B. Prevention and treatment of the common cold: making sense of the evidence. CMAJ. 2014; 186 (3): 190-9.

13. McKimm-Breschkin J.L. Influenza neuraminidase inhibitors: Antiviral action and mechanisms of resistance. Influenza Other Respir Viruses. 2012; 7 (Suppl. 1): 25-36.

14. Jefferson T., Rivetti A., Di Pietrantonj C., Demicheli V. Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev. 2018; 2: CD004879.

15. Demicheli V., Jefferson T., Ferroni E., Rivetti A., Di Pietrantonj C. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2018; 2: CD001269.

16. Demicheli V., Jefferson T., Di Pietrantonj C., Ferroni E., et al. Vaccines for preventing influenza in the elderly. Cochrane Database Syst Rev. 2018; 2: CD004876.

17. Jefferson T., Rivetti A., Di Pietrantonj C., Demicheli V. Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev. 2018; 2: CD004879.

18. Abbas A.T., El-Kafrawy S.A., Sohrab S.S., Azhar E.I.A. IgY antibodies for the immunoprophylaxis and therapy of respiratory infections. Hum Vaccin Immunother. 2019; 15 (1): 264-75.

19. Berry C.M. Antibody immunoprophylaxis and immunotherapy for influenza virus infection: Utilization of monoclonal or polyclonal antibodies? Hum Vaccin Immunother. 2018; 14 (3): 796-9.

20. Teijaro J.R. Type I interferons in viral control and immune regulation. Curr Opin Virol. 2016; 16: 31-40.

21. Singhania A., Graham C.M., Gabrysova L. Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases. Nat Commun. 2019; 10 (1): 2887.

22. The official instruction for medical use of the drug Ergoferon. http://grls.rosminzdrav.ru (access 11 October 2019) (in Russian)

23. Zhuravleva M.V., Kameneva T.R., Chernykh T.M., Chursina T.A. Comparative characteristics of drugs for the treatment of acute respiratory viral infection and influenza. Pediatrics (Doctor.Ru). 2015; (13): 11-8. (in Russian)

24. Andrianova E., Putilovskiy M. Efficacy and safety of Ergoferon versus oseltamivir: reply to the Letter to the Editor. Int J Infect Dis. 2019. pii: S1201-9712(19)30391-1. [Epub ahead of print] URL: https://pubmed.ncbi.nlm.nih.gov/31626982-efficacy-and-safety-of-ergoferon-versus-oseltamivir-reply-to-the-letter-to-the-editor/

doi: 10.1016/j.ijid.2019.09.028

25. Rafalsky V, Averyanov A, Bart B, Minina E, Putilovskiy M, Andrianova E, et al. Efficacy and safety of Ergoferon versus oseltamivir in adult outpatients with seasonal influenza virus infection: a multicenter, open-label, randomized trial. Int J Infect Dis.2016; 51: 47-55.

26. Selkova E.P., Kostinov M.P., Bart B.Ya., Averyanov A.V., Petrov D.V. Treatment of acute respiratory viral infections in adults: results of a randomized, double-blind, placebo-controlled clinical trial. Pulmonologiya [Pulmonology]. 2019; 29 (3): 302-10. (in Russian)

27. Kostinov M.P., Khamitov R.F., Babkin A.P., Minina E.S., et al. Treatment of acute respiratory infection in adults: results of a multicenter, randomized, double-blind, placebo-controlled clinical trial. Lechashchiy vrach [Attending Physician]. 2019 (10): 72-8. (in Russian)

28. Geppe N.A., Kondyurina E.G., Melnikova I.M., Sabitov A.U., et al. Release-active antiviral drug Ergoferon in the treatment of acute respiratory infections in children. The efficiency of liquid dosage form of Ergoferon: results of a randomized double-blind placebo-controlled clinical studies. Pediatriya. Zhurnal im. G.N. Speranskogo [Pediatrics. Journal named after G.N. Speranskiy]. 2019; 98 (1): 87-94. (in Russian)

29. Higgins J.P., Altman D.G., Gctzsche P.C., JQni P., et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011; 343: d5928.

30. Rebrova O.Yu., Fedyaeva V.C., Khachatryan G.R. Adaptation and validation of a questionnaire to assess the risk of systematic errors in randomized controlled trials. Meditsinskie tekhnologii. Otsenka i vybor [Medical Technology. Evaluation and Selection]. 2015; 1 (19): 9-17. (in Russian)

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CHIEF EDITOR
Aleksandr V. Gorelov
Academician of the Russian Academy of Sciences, MD, Head of Infection Diseases and Epidemiology Department of the Scientific and Educational Institute of Clinical Medicine named after N.A. Semashko ofRussian University of Medicine, Ministry of Health of the Russian Federation, Professor of the Department of Childhood Diseases, Clinical Institute of Children's Health named after N.F. Filatov, Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Deputy Director for Research, Central Research Institute of Epidemiology, Rospotrebnadzor (Moscow, Russian Federation)

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