An early assessment of the efficacy of medicines in the treatment of patients with COVID-19

Cover Page


Cite item

Full Text

Abstract

Coronavirus infection 2019 is considered a modern challenge to the world community. In the absence of vaccines and antivirals, effective and safe medicines are an urgent request from the healthcare system. We have evaluated the medical technologies for COVID-19 which are being examined. The search was conducted on the СlinicalTrials.gov at the beginning of April 2020. As a result it was shown that the growth of new clinical trials in the world devoted to COVID-19 is growing by 65% per week. More often, interventional clinical trials of the II and III phases are carried out. Most studies are planned or conducted in Western Europe (n = 92), China (n = 79), and the United States (n = 51). Surrogate points are usually evaluated, such as: clinical recovery, symptom-based disease relief (fever, cough, diarrhea, myalgia, shortness of breath), lack of progression of shortness of breath, rate of artificial ventilation, rate of admission to the intensive care unit, etc. It is antimalarial drugs that are mainly studied. Currently, it is not possible to discuss the efficacy and safety of a drug in the treatment of COVID-19, as most studies have just begun. The therapeutic regimens proposed now in clinical recommendations have no evidence base, and the studies indicated in them are at best considered hypothesizing.

About the authors

A. S. Kolbin

First Pavlov State Medical University of St.Petersburg; St. Petersburg State University

Author for correspondence.
Email: alex.kolbin@mail.ru
ORCID iD: 0000-0002-1919-2909

Aleksey S. Kolbin – PhD, MD (Medicine), Professor, Head of the Department of Clinical Pharmacology and Evidence-Based Medicine, Pavlov First St. Petersburg State Medical University; Professor of the Department of Pharmacology, Medical Faculty, St. Petersburg State University

Researcher ID (WOS) G-5537-2015
Author ID (Scopus) 19836020100
SPIN-код: 7966-0845

197022, St. Petersburg, L. Tolstoy str., 6/8
Phone: +7 921 759-04-49 

Russian Federation

References

  1. Вербицкая Е.В. Доказательная медицина: основные понятия, принципы поиска и оценки информации: Методическое пособие. Под ред. А.С. Колбина. СПб.: РИЦ ПСПбГМУ, 2017. 36 с.
  2. Галанкин Т.Л., Вербицкая Е.В. Фармакоэпидемиология: Методическое пособие. Под ред. А.С. Колбина. СПб.: Издательство СПбГМУ, 2015. 40 с.
  3. Оценка медицинских технологий, 2013 г. Под общ. ред. Ю.Б. Белоусова. М.: Издательство ОКИ, 2013. 40 с.
  4. Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19): Временные методические рекомендации. Версия 4 (27.03.2020). URL: https://static-3.rosminzdrav.ru/system/attachments/attaches/000/049/877/original/COVID19_recomend_v4.pdf
  5. Управление клиническими исследованиями. Под общ. ред. Д.Ю. Белоусова, С.К. Зырянова, А.С. Колбина. 1-е изд. М.: Буки Веди: Издательство ОКИ, 2017. 676 с.
  6. Шкурупий В.А., Курунов Ю.Н., Яковченко Н.Н. Лизосомотропизм — проблемы клеточной физиологии и медицины. Новосибирск: Издательство Новосибирского государственного медицинского университета, 1999. 289 с.
  7. Alhazzani W., M øller M.H., Arabi Y.M., Loeb M., Gong M.N., Fan E., Oczkowski S., Levy M.M., Derde L., Dzierba A., Du B., Aboodi M., Wunsch H., Cecconi M., Koh Y., Chertow D.S., Maitland K., Alshamsi F., Belley-Cote E., Greco M., Laundy M., Morgan J.S., Kesecioglu J., McGeer A., Mermel L., Mammen M.J., Alexander P.E., Arrington A., Centofanti J.E., Citerio G., Baw B., Memish Z.A., Hammond N., Hayden F.G., Evans L., Rhodes A. Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit. Care Med., 2020. doi: 10.1097/CCM.0000000000004363
  8. Aronson J.K., Ferner R.E. Drugs and the renin-angiotensin system in COVID-19. BMJ, 2020, vol. 369: m1313. doi: 10.1136/bmj.m1313
  9. Berthet J. Scientific work of Christian de Duve. Bull. Mem. Acad. R. Med. Belg., 2007, vol. 162, no. 10–12, pp. 499–504.
  10. Cao B., Wang Y., Wen D., Liu W., Wang J., Fan G., Ruan L., Song B., Cai Y., Wei M., Li X., Xia J., Chen N., Xiang J., Yu T., Bai T., Xie X., Zhang L., Li C., Yuan Y., Chen H., Li H., Huang H., Tu S., Gong F., Liu Y., Wei Y., Dong C., Zhou F., Gu X., Xu J., Liu Z., Zhang Y., Li H., Shang L., Wang K., Li K., Zhou X., Dong X., Qu Z., Lu S., Hu X., Ruan S., Luo S., Wu J., Peng L., Cheng F., Pan L., Zou J., Jia C., Wang J., Liu X., Wang S., Wu X., Ge Q., He J., Zhan H., Qiu F., Guo L., Huang C., Jaki T., Hayden F.G., Horby P.W., Zhang D., Wang C. A trial of lopinavir-ritonavir in adults hospitalized with severe COVID-19. N. Engl. J. Med., 2020. doi: 10.1056/NEJMoa2001282
  11. CDC. Coronavirus (COVID-19). URL: https://www.cdc.gov/coronavirus/2019-nCoV/index.html
  12. CDC. Severe Acute Respiratory Syndrome (SARS). URL: https://www.cdc.gov/sars
  13. Chan J.F., Yao Y., Yeung M.L., Deng W., Bao L., Jia L., Li F., Xiao C., Gao H., Yu P., Cai J.P., Chu H., Zhou J., Chen H., Qin C., Yuen K.Y. Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset. J. Infect. Dis., 2015, vol. 212, pp. 1904–1913. doi: 10.1093/infdis/jiv392
  14. Cochrane Library. Coronavirus (COVID-19). URL: https://www.cochranelibrary.com/covid-19
  15. Coronavirus disease 2019 (COVID-19): a guide for U.K. GPs. BMJ, 2020, vol. 368: m800. doi: 10.1136/bmj.m800
  16. De Wilde A.H., Jochmans D., Posthuma C.C., Zevenhoven-Dobbe J.C., van Nieuwkoop S., Bestebroer T.M., van den Hoogen B.G., Neyts J., Snijder E.J. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob. Agents Chemother., 2014, vol. 58, pp. 4875–4884.
  17. Delang L., Abdelnabi R., Neyts J. Favipiravir as a potential countermeasure against neglected and emerging RNA viruses. Antiviral Res., 2018, vol. 153, pp. 85–94. doi: 10.1016/j.antiviral.2018.03.003
  18. European Medicines Agency. COVID-19: chloroquine and hydroxychloroquine only to be used in clinical trials or emergency use programmes. URL: https://www.ema.europa.eu/en/news/covid-19-chloroquine-hydroxychloroquine-only-be-used-clinical-trialsemergency-use-programmes
  19. Falzarano D., de Wit E., Rasmussen A.L., Feldmann F., Okumura A., Scott D.P., Brining D., Bushmaker T., Martellaro C., Baseler L., Benecke A.G., Katze M.G., Munster V.J., Feldmann H. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat. Med., 2013, vol. 19, pp. 1313–1317. doi: 10.1038/nm.3362
  20. Fludase — Experimental Antiviral Drug for Influenza. URL: https://www.clinicaltrialsarena.com/projects/fludase
  21. Garcia Borrega J., G ö del P., R ü ger M.A., Onur Ö .A., Shimabukuro-Vornhagen A., Kochanek M., B ö ll B. In the eye of the storm: immune-mediated toxicities associated with CAR-T cell therapy. HemaSphere, 2019, vol. 3, no. 2: e191. doi: 10.1097/HS9.0000000000000191
  22. Holshue M.L., DeBolt C., Lindquist S., Lofy K.H., Wiesman J., Bruce H., Spitters C., Ericson K., Wilkerson S., Tural A., Diaz G., Cohn A., Fox L., Patel A., Gerber S.I., Kim L., Tong S., Lu X., Lindstrom S., Pallansch M.A., Weldon W.C., Biggs H.M., Uyeki T.M., Pillai S.K.; Washington State-nCoV Case Investigation Team. First case of 2019 novel Coronavirus in the United States. N. Engl. J. Med., 2020, vol. 382, pp. 929–936. doi: 10.1056/NEJMoa2001191
  23. Keyaerts E., Vijgen L., Maes P., Neyts J., Van Ranst M. In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem. Biophys. Res. Commun., 2004, vol. 323, pp. 264–268. doi: 10.1016/j.bbrc.2004.08.085
  24. Marjuki H., Mishin V.P., Chesnokov A.P., De La Cruz J.A., Fry A.M., Villanueva J., Gubareva L.V. An investigational antiviral drug, DAS181, effectively inhibits replication of zoonotic influenza A virus subtype H7N9 and protects mice from lethality. J. Infect. Dis., 2014, vol. 210, no. 3, pp. 435-440. doi: 10.1093/infdis/jiu105
  25. Markham A., Keam S.J. Danoprevir: first global approval. Drugs, 2018, vol. 78, no. 12, pp. 1271–1276. doi: 10.1007/s40265-018-0960-0
  26. McChesney E.W. Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate. Am. J. Med., 1983, vol. 75, pp. 11–18. doi: 10.1016/0002-9343(83)91265-2
  27. Mingo R.M., Simmons J.A., Shoemaker C.J., Nelson E.A., Schornberg K.L., D’Souza R.S., Casanova J.E., White J.M. Ebola virus and severe acute respiratory syndrome coronavirus display late cell entry kinetics: evidence that transport to NPC1+ endolysosomes is a rate-defining step. J. Virol., 2015, vol. 89, pp. 2931–2943. doi: 10.1128/JVI.03398-14
  28. Mulangu S., Dodd L.E., Davey R.T. Jr, Tshiani Mbaya O., Proschan M., Mukadi D., Lusakibanza Manzo M., Nzolo D., Tshomba Oloma A., Ibanda A., Ali R., Coulibaly S., Levine A.C., Grais R., Diaz J., Lane H.C., Muyembe-Tamfum J.J.; PALM Writing Group, Sivahera B., Camara M., Kojan R., Walker R., Dighero-Kemp B., Cao H., Mukumbayi P., Mbala-Kingebeni P., Ahuka S., Albert S., Bonnett T., Crozier I., Duvenhage M., Proffitt C., Teitelbaum M., Moench T., Aboulhab J., Barrett K., Cahill K., Cone K., Eckes R., Hensley L., Herpin B., Higgs E., Ledgerwood J., Pierson J., Smolskis M., Sow Y., Tierney J., Sivapalasingam S., Holman W., Gettinger N., Vallée D., Nordwall J; PALM Consortium Study Team. A randomized, controlled trial of Ebola virus disease therapeutics. N. Engl. J. Med., 2019, vol. 381, pp. 2293–2303. doi: 10.1056/NEJMoa1910993
  29. Patel A.B, Verma A. COVID-19 and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. What is the evidence? JAMA, 2020. doi: 10.1001/jama.2020.4812
  30. Savarino А., Trani D., Donatelli I., Cauda R., Cassone A. New insights into the antiviral effects of chloroquine. Lancet Infect. Dis., 2006, vol. 6, pp. 67–69. doi: 10.1016/S1473-3099(06)70361-9
  31. Schrezenmeier E., Dorner Е. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat. Rev. Rheumatol., 2020, vol. 16, pp. 155–166. doi: 10.1038/s41584-020-0372-x
  32. Sheahan T.P., Sims A.C., Leist S.R., Schä fer A., Won J., Brown A.J., Montgomery S.A., Hogg A., Babusis D., Clarke M.O., Spahn J.E., Bauer L., Sellers S., Porter D., Feng J.Y., Cihlar T., Jordan R., Denison M.R., Baric R.S. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat. Commun., 2020, vol. 11, no. 1: 222. doi: 10.1038/s41467-019-13940-6
  33. Tchesnokov E., Feng Y., Porter D., Gö tte M. Mechanism of inhibition of Ebola virus RNA-dependent RNA Polymerase by remdesivir. Viruses, 2019, vol. 11, no. 4: E326. doi: 10.3390/v11040326
  34. Vincent M.J., Bergeron E., Benjannet S., Erickson B.R., Rollin P.E., Ksiazek T.G., Seidah N.G., Nichol S.T. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol. J., 2005, vol. 2: 69. doi: 10.1186/1743-422X-2-69
  35. WHO. Coronavirus disease (COVID-19) Pandemic. URL: https://www.who.int/emergencies/diseases/novel-coronavirus-2019
  36. Yao T.T., Qian J.D., Zhu W.Y., Wang Y., Wang G.Q. A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus — a possible reference for coronavirus disease-19 treatment option. J. Med. Virol., 2020. doi: 10.1002/jmv.25729
  37. Yao X., Ye F., Zhang M., Cui C., Huang B., Niu P., Liu X., Zhao L., Dong E., Song C., Zhan S., Lu R., Li H., Tan W., Liu D. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin. Infect. Dis., 2020: ciaa237. doi: 10.1093/cid/ciaa237
  38. Yazdany J., Kim A.H.J. Use of hydroxychloroquine and chloroquine during the COVID-19 pandemic: what every clinician should know. Ann. Intern. Med., 2020. doi: 10.7326/M20-1334
  39. Zhai P., Ding Y., Wu X., Long J., Zhong Y., Li Y. The epidemiology, diagnosis and treatment of COVID-19. Int. J. Antimicrob. Agents, 2020: 105955. doi: 10.1016/j.ijantimicag.2020.105955
  40. Zhou P., Yang X.L., Wang X.G., Hu B., Zhang L., Zhang W., Si H.R., Zhu Y., Li B., Huang C.L., Chen H.D., Chen J., Luo Y., Guo H., Jiang R.D., Liu M.Q., Chen Y., Shen X.R., Wang X., Zheng X.S., Zhao K., Chen Q.J., Deng F., Liu L.L., Yan B., Zhan F.X., Wang Y.Y., Xiao G.F., Shi Z.L. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020, vol. 579, no. 7798, pp. 270–273. doi: 10.1038/s41586-020-2012-7

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2020 Kolbin A.S.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 64788 от 02.02.2016.


This website uses cookies

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

About Cookies