The effect of etiopathogenetic therapy of COVID-19 on the severity of the disease: results of a multicenter double-blind placebo-controlled randomized trial

Cover Page

Cite item

Full Text

Abstract

Aim. The search for etiopathogenetic agents to prevent the development of severe and extremely severe COVID-19 remains relevant. A placebo-controlled randomized clinical trial was conducted to evaluate the efficacy and safety of the antibody-based biological drug (Raphamin).
Materials and methods. 785 outpatients 18–75 y.o. with laboratory confirmed mild COVID-19 were included within 24 hours from the disease onset. 771 patients were randomized to the group Raphamin (n=382) and the Placebo group (n=389). The study drug/placebo was prescribed for 5 days. The rate of progression to a more severe degree of COVID-19 by day 28 as well as the time to sustained clinical recovery and the frequency of hospitalization were evaluated. Safety was assessed taking into account adverse events, vital signs and laboratory parameters.
Results. The number of cases of progression to a more severe degree of COVID-19 in participants receiving Raphamin was 59 (15.5%) [52 (14.6%)] versus placebo – 89 (22.9%) [85 (23.7%)], ITT and [PP] analysis data are presented. The odds ratio between groups was OR=0.6157 [OR=0.5494], 95% confidence interval 0.4276–0.8866 [0.3750–0.8048], which meant a reduction in the chance of progression to a more severe degree by 38.4% [45.1%] or 1.48 [1.62] times; p=0.0088 [p=0.0019]. The time to sustained recovery in the Raphamin group was 4.5±2.4 [4.6±2.4] days, versus placebo – 5.8±4.7 [6.0±4.8] days; p=0.0025 [p=0.0036]. No adverse events with a certain relationship were registered.
Conclusion. Raphamin reduces the risk of progression to a more severe degree of the COVID-19 and significantly shortens the duration of clinical symptoms.

About the authors

Vladimir V. Nikiforov

Pirogov Russian National Research Medical University; Federal Scientific and Clinical Center for Specialized Types of Medical Care and Medical Technologies

Email: vapetrov1959@mail.ru
ORCID iD: 0000-0002-2205-9674

доктор медицинских наук, профессор, зав. кафедры инфекционных болезней и эпидемиологии лечебного факультета, зав. кафедры инфекционных болезней и эпидемиологии Академии постдипломного образования

Russian Federation, Moscow; Moscow

Vladimir A. Petrov

Obninsk Institute for Nuclear Power Engineering – branch of National Research Nuclear University „MEPhI“

Email: vapetrov1959@mail.ru
ORCID iD: 0000-0002-8580-933X

доктор медицинских наук, зав. кафедры инфекционных болезней, общественного здоровья и здравоохранения

Russian Federation, Obninsk

Anatoly A. Stremoukhov

Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: vapetrov1959@mail.ru
ORCID iD: 0000-0002-4393-3543

доктор медицинских наук, профессор, директор Института методологии профессионального развития, зав. кафедры общей врачебной практики и поликлинической терапии

Russian Federation, Moscow

Marina G. Avdeeva

Kuban State Medical University

Email: vapetrov1959@mail.ru
ORCID iD: 0000-0002-4979-8768

доктор медицинских наук, профессор кафедры инфекционных болезней и фтизиопульмонологии

Russian Federation, Krasnodar

Yury G. Shvarts

Razumovsky Saratov State Medical University

Email: vapetrov1959@mail.ru
ORCID iD: 0000-0002-5205-7311

доктор медицинских наук, профессор, зав. кафедры факультетской терапии лечебного факультета

Russian Federation, Saratov

Irina E. Kravchenko

Kazan State Medical University

Email: vapetrov1959@mail.ru
ORCID iD: 0000-0003-4408-7542

доктор медицинских наук, доцент, профессор кафедры инфекционных болезней

Russian Federation, Kazan

Irina V. Nikolaeva

Kazan State Medical University

Email: vapetrov1959@mail.ru
ORCID iD: 0000-0003-0104-5895

доктор медицинских наук, доцент, зав. кафедры инфекционных болезней

Russian Federation, Kazan

Svetlana E. Ushakova

Kuvaevs Ivanovo Clinical Hospital; Ivanovo State Medical Academy

Email: vapetrov1959@mail.ru
ORCID iD: 0000-0002-8903-0948

доктор медицинских наук, доцент, врач-трапевт, зав. кафедры поликлинической терапии и эндокринологии

Russian Federation, Ivanovo; Ivanovo

Oksana N. Belousova

Belgorod State University

Email: vapetrov1959@mail.ru
ORCID iD: 0000-0001-6862-0829

доктор медицинских наук, доцент, профессор кафедры госпитальной терапии, глав. врач поликлиники

Russian Federation, Belgorod

Natal'ia A. Eremina

Clinical Hospital RZhD Medicina

Email: vapetrov1959@mail.ru
ORCID iD: 0000-0002-6395-1730

кандидат медицинских наук, клин. фармаколог

Russian Federation, Nizhnii Novgorod

Svetlana V. Teplykh

„Professor clinic“ LLC

Email: vapetrov1959@mail.ru
ORCID iD: 0000-0003-1997-7279

кандидат медицинских наук, генеральный директор

Russian Federation, Perm

Ekaterina V. Mel'nikova

„Medical center for diagnostics and prevention “ LLC

Email: vapetrov1959@mail.ru
ORCID iD: 0000-0003-3352-5949

кандидат медицинских наук, зам. ген. дир. по научной работе, врач-терапевт

Russian Federation, Iaroslav

Natal'ia E. Kostinа

Voronezh Regional Clinic Hospital №1

Email: vapetrov1959@mail.ru
ORCID iD: 0000-0002-5128-5005

кандидат медицинских наук, зав. пульмонологическим отделением

Russian Federation, Voronezh

References

  1. COVID-19 Coronavirus Pandemic. Weekly Trends. Available at: https://www.worldometers.info/coronavirus Accessed: 29.09.2023.
  2. Акимкин В.Г., Попова А.Ю., Плоскирева А.А., и др. COVID-19: эволюция пандемии в России. Сообщение I: проявления эпидемического процесса COVID-19. Журнал микробиологии, эпидемиологии и иммунобиологии. 2022;99(3):269-86 [Akimkin VG, Popova AYu, Ploskireva AA, et al. COVID-19: the evolution of the pandemic in Russia. Report I: manifestations of the COVID-19 epidemic process. Journal of Microbiology, Epidemiology and Immunobiology. 2022;99(3):269-86 (in Russian)]. doi: 10.36233/0372-9311-276
  3. Петрова Н.В., Емельянова А.Г., Ковальчук А.Л., Тарасов С.А. Роль молекул MHC I и II в антибактериальном иммунитете и лечении бактериальных инфекций. Антибиотики и Химиотерапия. 2022;67(7–8):71-81 [Petrova NV, Emelyanova AG, Kovalchuk AL,Tarasov SA. The role of MHC class I and class II molecules in antibacterial immunity and treatment of bacterial diseases. Antibiotics and Chemotherapy. 2022;67(7–8):71-81 (in Russian)]. doi: 10.37489/0235-2990-2022-67-7-8-71-81
  4. Рафамин. Общая характеристика лекарственного препарата. Единый реестр зарегистрированных лекарственных средств Евразийского экономического союза. Режим доступа: https://portal.eaeunion.org/sites/commonprocesses/ru-ru/Pages/DrugRegistrationDetails.aspx Ссылка активна на 29.09.2023 [Raphamin. Obshchaia kharakteristika lekarstvennogo preparata. Edinyi reestr zaregistrirovannykh lekarstvennykh sredstv Evraziiskogo ekonomicheskogo soiuza. Available at: https://portal.eaeunion.org/sites/commonprocesses/ru-ru/Pages/DrugRegistrationDetails.aspx Accessed: 29.09.2023 (in Russian)].
  5. Хамитов Р.Ф., Никифоров В.В., Зайцев А.А., Трагира ИН. Оценка эффективности и безопасности комплексного противовирусного препарата на основе антител в терапии острой респираторной вирусной инфекции у взрослых. Терапевтический архив. 2022;94(1):83-93 [Khamitov RF, Nikiforov VV, Zaytsev AA, Tragira IN. Evaluation of the efficacy and safety of a complex antiviral drug based on antibodies in the treatment of adult patients with acute respiratory viral infection. Terapevticheskii Arkhiv (Ter. Arkh.). 2022;94(1):83-93 (in Russian)]. doi: 10.26442/00403660.2022.01.201345
  6. Development of the COVID-19 infection model: a preclinical study of a new drug Rafamin. Available at: https://www.vibiosphen.com/development-covid-19-infection-model-preclinical-study-new-drug-rafamin Accessed: 29.09.2023.
  7. Assessing COVID-19-Related Symptoms in Outpatient Adult and Adolescent Subjects in Clinical Trials of Drugs and Biological Products for COVID-19 Prevention or Treatment: Guidance for Industry. Food and Drug Administration. September 2020. Available at: Assessing COVID-19-Related Symptoms in Outpatient Adult and Adolescent Subjects in Clinical Trials of Drugs and Biological Products for COVID-19 Prevention or Treatment (fda.gov) Accessed: 07.11.2023
  8. Saravolatz LD, Depcinski S, Sharma M. Molnupiravir and Nirmatrelvir-Ritonavir: Oral Coronavirus Disease 2019 Antiviral Drugs. Clin Infect Dis. 2023;76(1):165-71. doi: 10.1093/cid/ciac180
  9. Еникеева Д.А., Бондарчук Н.Г. Фармакологические вещества, проявляющие противовирусную активность в отношении коронавируса SARS-CoV-2. Экспериментальная и клиническая фармакология. 2022;85(7):13-22 [Enikeeva DA, Bondarchuk NG. Pharmacological agents with antiviral activity against coronavirus SARS-CoV-2. Experimental and clinical pharmacology. 2022;85(7):13-22 (in Russian)]. doi: 10.30906/0869-2092-2022-85-7-13-22
  10. Gupta A, Gonzalez-Rojas Y, Juarez E, et al. Early treatment for COVID-19 with SARS-CoV-2 neutralizing antibody sotrovimab. N Engl J Med. 2021;385(21):1941-50. doi: 10.1056/NEJMoa2107934
  11. Kim JY, Săndulescu O, Preotescu LL, et al. A Randomized Clinical Trial of Regdanvimab in High-Risk Patients With Mild-to-Moderate Coronavirus Disease 2019. Open Forum Infect Dis. 2022;9(8):ofac406. doi: 10.1093/ofid/ofac406
  12. Горелов А.В., Малявин А.Г., Антонова Е.А., и др. Оценка эффективности и безопасности противовирусной терапии COVID-19 препаратом имидазолилэтанамида пентандиовой кислоты: многоцентровое рандомизированное двойное слепое плацебо-контролируемое клиническое исследование. Инфекционные болезни. 2022;20(2):6-15 [Gorelov AV, Malyavin AG, Antonova EA, et al. Efficacy and safety of imidazolyl ethanamide pentandioic acid for COVID-19: a multicenter, randomized, double-blind, placebo-controlled clinical trial. Infectious Diseases. 2022;20(2):6-15 (in Russian)]. doi: 10.20953/1729-9225-2022-2-6-15
  13. Udwadia ZF, Singh P, Barkate H, et al. Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial. Int J Infect Dis. 2021;103:62-71. doi: 10.1016/j.ijid.2020.11.142
  14. Ершов Ф.И., Наровлянский А.Н. Проблема применения интерферонов при новой коронавирусной инфекции COVID-19 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus). Вопросы вирусологии. 2022;67(2):115-25 [Ershov FI, Narovlyansky AN. The problem of the use of interferons in the novel coronavirus disease COVID-19 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus). Vopr Virusol. 2022;67(2):115-25 (in Russian)]. doi: 10.36233/0507-4088-103

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Movement of patients during the study.

Download (379KB)
Indexing metadata
3. Fig. 2. Results for the primary efficiency criterion.

Download (70KB)
Indexing metadata
4. Fig. 3. Results for the secondary performance criterion.

Download (61KB)
Indexing metadata

Copyright (c) 2023 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies