Effectiveness and safety of favipiravir infusion in patients hospitalized with COVID-19
- Authors: Balykova L.A.1, Zaslavskaya K.Y.2, Pavelkina V.F.1, Pyataev N.A.1, Selezneva N.M.1, Kirichenko N.V.3, Ivanova A.Y.4,5, Rodoman G.V.6, Kolontarev K.B.7,8, Skrupsky K.S.8, Simakina E.N.9,10, Mubarakshina O.A.11, Taganov A.V.12, Pushkar D.Y.7,8
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Affiliations:
- National Research Ogarev Mordovia State University
- Limited Liability Company “Promomed RUS”
- Ivanovo Clinical Hospital named after the Kuvaevs
- Regional Clinical Hospital
- Ryazan State Medical University named after academician I.P. Pavlova
- Municipal clinical hospital No. 24, Moscow City Health Department
- Moscow State Medical and Dental University named after A.I. Evdokimov
- City Clinical Hospital named after S.I. Spasokukotsky, Moscow City Health Department
- Smolensk clinical hospital No.1
- Smolensk State Medical University
- Voronezh State Medical University named after N.N. Burdenko
- Peoples’ Friendship University
- Issue: Vol 10, No 1 (2022)
- Pages: 113-126
- Section: Articles
- URL: https://journals.rcsi.science/2307-9266/article/view/111732
- DOI: https://doi.org/10.19163/2307-9266-2022-10-1-113-126
- ID: 111732
Cite item
Abstract
Research in the development of new therapeutic agents with a wide spectrum of the antiviral activity and a low ability to develop resistance remains the main dimension in combating the global threat to public health. The need for a parenteral form of favipiravir was dictated by the necessity to increase the efficacy of therapy in COVID-19 inpatients. This dosage form has expanded the possibilities of drug therapy in the inpatients, for whom a therapeutic effect acceleration and a high safety profile of the drugs used are especially important.
The aim of the article is the evaluation of the efficacy and safety of a medicinal product containing favipiravir for the parenteral administration against the background of pathogenetic and symptomatic therapy, in comparison with standard therapy in hospitalized COVID-19 patients.
Materials and methods. An open, randomized, multicenter comparative study was conducted in 6 research centers in the Russian Federation to evaluate the efficacy and safety of favipiravir, a lyophilisate for the preparation of a concentrate for the infusion solution administrated to the patients hospitalized with COVID-19. Screening procedures and randomization were completed in 217 patients, 209 of which had completed the study in accordance with the protocol.
Results. Between the study groups, statistically significant differences have been found out, making it possible to consider the hypothesis of the drug Areplivir (favipiravir) superiority for the parenteral administration over the standard therapy, which included favipiravir (p. o.) and remdesivir. A comparative analysis has shown that a course of therapy with the parenteral favipiravir drug leads to a significant improvement in the condition of patients with COVID-19, significant benefits in terms of the speed and frequency of improvement in the clinical status of patients, as well as a reduction in the hospital stay length. It has been proven that therapy with a drug containing favipiravir for the parenteral administration does not adversely affect the parameters of clinical and biochemical blood tests, urinalysis, coagulograms, vital signs and ECG, which indicates the therapy safety. The study drug is characterized by a high safety profile and tolerability.
Conclusion. The versatility and resistance to mutations of RNA-dependent RNA polymerase make it possible to consider it as the main target for combating the most common RNA viruses that cause ARVI, that determines the need further studies of favipiravir to expand the range of its indications.
Abbreviations: COVID-19 – novel coronavirus infection (Coronavirus disease 2019); AV – Artificial ventilation; GIT – gastrointestinal tract; ECMO – Extracorporeal membrane oxygenation; ITT – population of all included (Intent-to-treat) patients; PP – the population of patients who completed the study according to the protocol (Per protocol); NAATs – nucleic acid amplification techtiques; NYHA – New York Heart Association; e-IRK – electronic individual registration card; ARDS – Acute Respiratory Distress Syndrome; CRP – c-reactive protein; ESR – erythrocyte sedimentation rate; NAATs – Nucleic Acid Amplification Techniques; GIT – gastrointestinal tract; HR – heart rate; AspAT – aspartate transaminase; ALT – alanine aminotransferase; ULN – upper limit of normal; UDE – undesirable effects; IGs – Interim Guidelines; NSAIDs – non-steroidal anti-inflammatory drugs; GGT – gamma-glutamyl transpeptidase; CK – creatine kinase.
Keywords
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##article.viewOnOriginalSite##About the authors
Larisa A. Balykova
National Research Ogarev Mordovia State University
Email: larisabalykova@yandex.ru
ORCID iD: 0000-0002-2290-0013
Corresponding Member of the Russian Academy of Sciences, Doctor of Sciences (Medicine), Professor, Head of the Department of Pediatrics, Director of the Medical Institute
Russian Federation, 68, Bol’shevistskaya Str., Saransk, Republic of Mordovia, 430005Kira Ya. Zaslavskaya
Limited Liability Company “Promomed RUS”
Email: kiryonok@yandex.ru
ORCID iD: 0000-0002-7348-9412
Director of New Products
Russian Federation, Bld. 1, 13, Mir Ave., Moscow, 129090Vera F. Pavelkina
National Research Ogarev Mordovia State University
Email: pavelkina@rambler.ru
ORCID iD: 0000-0001-9582-9986
Doctor of Sciences (Medicine), Professor, Head of the Department of Infectious Diseases with courses in Epidemiology, Phthisiology, Skin and Venereal Diseases
Russian Federation, 68, Bol’shevistskaya Str., Saransk, Republic of Mordovia, 430005Nikolai A. Pyataev
National Research Ogarev Mordovia State University
Email: pyataevna@mail.ru
ORCID iD: 0000-0002-9688-7640
Doctor of Sciences (Medicine), Associate Professor, Head of the Department of Anesthesiology and Resuscitation
Russian Federation, 68, Bol’shevistskaya Str., Saransk, Republic of Mordovia, 430005Natalya M. Selezneva
National Research Ogarev Mordovia State University
Email: nata_rm@mail.ru
ORCID iD: 0000-0002-3004-2063
Candidate of Sciences (Medicine), Associate Professor of the Department of Hospital Therapy
Russian Federation, 68, Bol’shevistskaya Str., Saransk, Republic of Mordovia, 430005Natalya V. Kirichenko
Ivanovo Clinical Hospital named after the Kuvaevs
Email: igb2@ivreg.ru
ORCID iD: 0000-0002-4272-9540
Deputy Chief Physician of the Medical Department
Russian Federation, Bld. 2, 52, Ermak Str., Ivanovo, 153025Anastasia Yu. Ivanova
Regional Clinical Hospital; Ryazan State Medical University named after academician I.P. Pavlova
Email: Nastya_doctor@list.ru
ORCID iD: 0000-0002-4112-5382
Assistant of the Department of Faculty Therapy, anesthesiologist
Russian Federation, Bld. A, 3, Internatsionalnaya Str., Ryazan, 390039; 9, Vysokovoltnaya Str., Ryazan, 390026Grigory V. Rodoman
Municipal clinical hospital No. 24, Moscow City Health Department
Email: generalsurgery24@mail.ru
ORCID iD: 0000-0001-6692-1425
Doctor of Sciences (Medicine), Chief Physician
Russian Federation, 10, Pistsovaya Str., Moscow, 127015Konstantin B. Kolontarev
Moscow State Medical and Dental University named after A.I. Evdokimov; City Clinical Hospital named after S.I. Spasokukotsky, Moscow City Health Department
Email: kb80@yandex.ru
ORCID iD: 0000-0003-4511-5998
Doctor of Sciences (Medicine), Professor, Department of Urology, Head of the Oncourological Department
Russian Federation, Bld. 1, 20, Delegatskaya Str., Moscow, 127473; 21, Vuchetich Str., Moscow, 127206Konstantin S. Skrupsky
City Clinical Hospital named after S.I. Spasokukotsky, Moscow City Health Department
Email: 89_sks@mail.ru
ORCID iD: 0000-0001-6651-8142
urologist, oncourological Department
Russian Federation, 21, Vuchetich Str., Moscow, 127206Elena N. Simakina
Smolensk clinical hospital No.1; Smolensk State Medical University
Email: e.simakina@mail.ru
ORCID iD: 0000-0002-5709-8913
Candidate of Sciences (Medicine), Head of the Infectious Diseases Department, Assistant of the Department of Infectious Diseases
Russian FederationOlga A. Mubarakshina
Voronezh State Medical University named after N.N. Burdenko
Email: mubarakshina@mail.ru
ORCID iD: 0000-0001-6799-6322
Candidate of Sciences (Medicine), Associate Professor of the Department of Clinical Pharmacology
Russian Federation, 10, Studencheskaya Str., Voronezh, 394036Aleksey V. Taganov
Peoples’ Friendship University
Email: matis87177@yandex.ru
ORCID iD: 0000-0001-5056-374X
Doctor Sciences (Medicine), Professor of the Department of Dermatovenereology with a course of cosmetology of the Faculty of Continuous Medical Education
Russian Federation, 6, Miklukho Maclaya Str., Moscow, 117198Dmitry Yu. Pushkar
Moscow State Medical and Dental University named after A.I. Evdokimov; City Clinical Hospital named after S.I. Spasokukotsky, Moscow City Health Department
Author for correspondence.
Email: pushkardm@mail.ru
ORCID iD: 0000-0002-6096-5723
Academician of the Russian Academy of Sciences, Doctor of Sciences (Medicine), Professor, Head of the Department of Urology, urologist
Russian Federation, Bld. 1, 20, Delegatskaya Str., Moscow, 127473; 21, Vuchetich Str., Moscow, 127206References
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