FAVIPIRAVIR EFFICACY AND SAFETY FOR THE TREATMENT OF SEVERE CORONAVIRUS 2019. A RETROSPECTIVE STUDY.

Authors

  • Waleed Aletreby King Saud Medical City
  • Basheer Abdulrahman
  • Ahmed Mady
  • Mohammed Al-Odat
  • Ashraf Al Tayar
  • Muhammad Asim Rana
  • Abdulrahman Alharthy
  • Alyaa Alhazmi
  • Ahmed Abdelmoaty
  • Muhammad Mansoor Hafeez
  • Ahmed Kuhail
  • Alfateh Noor
  • Mohammed Haddad
  • Anas Mady
  • Noor Ali

DOI:

https://doi.org/10.55519/JAMC-03-10305

Keywords:

Favipiravir, COVID-19, ICU, Efficacy, Safety

Abstract

Background: Corona virus disease is caused by the enveloped, single stranded RNA virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becoming the deadliest disease of the century. Its global outbreak has led researchers to develop drugs or vaccines to prevent the spread of the disease. Favipiravir is an approved orally administered antiviral drug that selectively inhibits RNA-dependent RNA polymerase, used off-label to treat COVID-19. Objectives: The purpose of this study was to assess the efficacy and safety of this drug for severe COVID-19 infection. Methods: This was an observational retrospective study, carried out at the ICU of King Saud Medical City (KSMC) from June 2020 to August 2020. Including a total of one thousand six hundred and ninety-nine patients (n=1699). Categorized into a treatment group (193 patients) who received Favipiravir along with standard care, and non-treatment group (1506 patients) who received standard care only. Results: ICU all-cause mortality was similar in both groups i.e., (Treated group 38.3% Vs Untreated group 39.4%, 95% CI of difference: -6.6% to +8.4%; p = 0.8). The subgroup analysis of survivors as compared to deceased in the treatment group showed that survivors had significantly lower age, international normalising ratio (INR), blood urea nitrogen (BUN), and creatinine. The mean ICU length of stay (LOS) was shorter for survivors compared to deceased (11.2± 8.03 Vs 16.7±9.8 days respectively), while hospital LOS was almost similar between the two groups. Advanced age (OR 1.03 [95% CI: 1.01–1.06]; p=0.004), higher INR and BUN were significantly associated with increased odds of mortality. Comparison of lab investigations at day 1 and day 10 in the treatment group (regardless of outcome) showed that there was a significant increase in Alanine transaminase (ALT), alkaline phosphatase (ALK), and Bilirubin, while an insignificant trend of increase in Aspartate transaminase (AST) and creatinine was recorded. Conclusion: In this study, Favipiravir showed better therapeutic responses in patients with severe COVID-19 infection, in terms of average duration of stay in the intensive care unit and was well tolerated in the younger age, but showed no mortality benefit. However, elevated levels of inflammatory markers, including increased ALT, AST, BUN, bilirubin, and creatinine, needs to be carefully examined.

References

Aletreby WT, Alharthy AM, Faqihi F, Mady AF, Ramadan OE, Huwait BM, et al. Dynamics of SARS-CoV-2 outbreak in the Kingdom of Saudi Arabia: A predictive model. Saudi Crit Care J 2020;4(2):79–83.

Gallegos A. WHO declares public health emergency for novel coronavirus. [Internet]. Medscape Medical News 2020. [cited 2021 Oct]. Available from: https://www.medscape.com/viewarticle/924596

Wee SL, McNeil D, Hernández JC. WHO declares global emergency as Wuhan coronavirus spreads. New York Times. 2020.

Bergman S. COVID-19 treatment: investigational drugs and other therapies. Medscape; 2021.

Alhazzani W, Møller MH, Arabi YM, Loeb M, Gong MN, Fan E, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med 2020;46(5):854–87.

Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. JAMA 2020;323(18):1824–36.

Idda ML, Soru D, Floris M. Overview of the first 6 months of clinical trials for COVID-19 pharmacotherapy: the most studied drugs. Front Public Health 2020;8:497.

Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, Cheng VC, et al. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Clin Infect Dis 2020;2020:ciaa478.

Jomah S, Asdaq SMB, Al-Yamani MJ. Clinical efficacy of antivirals against novel coronavirus (COVID-19): A review. J Infect Public Health 2020;13(9):1187–95.

Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA 2020;323(11):1061–9.

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395(10223):507–13.

Food U, Administration D. FDA approves first treatment for COVID-19. Food and Drug Administration news release Published October. 2020.

Marks M. Controlled Substance Regulation for the COVID-19 Mental Health Crisis. 2020.

Talukdar D, Jain V, Balaramnavar V, Srivastava SP, Sivanandy P, Gupta MM. Potential Drugs for COVID-19 Treatment Management With Their Contraindications and Drug-Drug Interaction. 2021.

Food, Administration D. Fact sheet for health care providers Emergency Use Authorization (EUA) of Bamlanivimab. 2021

Hassanipour S, Arab-Zozani M, Amani B, Heidarzad F, Fathalipour M, Martinez-de-Hoyo R. The efficacy and safety of Favipiravir in treatment of COVID-19: A systematic review and meta-analysis of clinical trials. Sci Rep 2021;11(1):1–11.

Kaur RJ, Charan J, Dutta S, Sharma P, Bhardwaj P, Sharma P, et al. Favipiravir use in COVID-19: Analysis of suspected adverse drug events reported in the WHO database. Infect Drug Resist 2020;13:4427.

Joshi S, Parkar J, Ansari A, Vora A, Talwar D, Tiwaskar M, et al. Role of favipiravir in the treatment of COVID-19. Int J Infect Dis 2020;102:501–8.

Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci 2017;93(7):449–63.

Dabbous HM, Abd-Elsalam S, El-Sayed MH, Sherief AF, Ebeid FFS, El Ghafar MSA, et al. Efficacy of favipiravir in COVID-19 treatment: a multi-center randomized study. Arch Virol 2021;166(3):949–54.

Ivashchenko AA, Dmitriev KA, Vostokova NV, Azarova VN, Blinow AA, Egorova AN, et al. AVIFAVIR for Treatment of Patients With Moderate Coronavirus Disease 2019 (COVID-19): Interim Results of a Phase II/III Multicenter Randomized Clinical Trial. Clin Infect Dis 2021;73(3):531–4.

Udwadia ZF, Singh P, Barkate H, Patil S, Rangwala S, Pendse A, 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.

Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering (Beijing) 2020;6(10):1192–8.

Dabbous HM, El-Sayed MH, El Assal G, Elghazaly H, Ebeid FFS, Sherief AF, et al. Safety and efficacy of favipiravir versus hydroxychloroquine in management of COVID-19: A randomised controlled trial. Sci Rep 2021;11(1):7282.

Alharthy A, Aletreby W, Faqihi F, Balhamar A, Alaklobi F, Alanezi K, et al. Clinical Characteristics and Predictors of 28-Day Mortality in 352 Critically Ill Patients with COVID-19: A Retrospective Study. J Epidemiol Glob Health 2021;11(1):98–104.

Mumtaz SA, Shahzad SA, Ahmed I, Alodat MA, Gharba M, Saif ZA, et al. External validation of 4C ISARIC mortality score in the setting of a Saudi Arabian ICU. Retrospective study. medRxiv 2021;8(16):21262104.

Zhao H, Zhang C, Zhu Q, Chen X, Chen G, Sun W, et al. Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: A multicenter, open-label, randomized trial. Int Immunopharmacol 2021;97:107702.

Published

2022-06-21