Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial
Viravarn Luvira, William H K Schilling, Podjanee Jittamala, James A Watson, Simon Boyd, Tanaya Siripoon, Thundon Ngamprasertchai, Pedro J Almeida, Maneerat Ekkapongpisit, Cintia Cruz, James J Callery, Shivani Singh, Runch Tuntipaiboontana, Varaporn Kruabkontho, Thatsanun Ngernseng, Jaruwan Tubprasert, Mohammad Yazid Abdad, Srisuda Keayarsa, Wanassanan Madmanee, Renato S Aguiar, Franciele M Santos, Pongtorn Hanboonkunupakarn, Borimas Hanboonkunupakarn, Kittiyod Poovorawan, Mallika Imwong, Walter R J Taylor, Vasin Chotivanich, Kesinee Chotivanich, Sasithon Pukrittayakamee, Arjen M Dondorp, Nicholas P J Day, Mauro M Teixeira, Watcharapong Piyaphanee, Weerapong Phumratanaprapin, Nicholas J White
BMC Infectious Diseases, doi:10.1186/s12879-023-08835-3
Brief summary In early symptomatic COVID-19 treatment, high dose oral favipiravir did not accelerate viral clearance. Background Favipiravir, an anti-influenza drug, has in vitro antiviral activity against SARS-CoV-2. Clinical trial evidence to date is inconclusive. Favipiravir has been recommended for the treatment of COVID-19 in some countries.
Methods In a multicentre open-label, randomised, controlled, adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomised to one of ten treatment arms including high dose oral favipiravir (3.6g on day 0 followed by 1.6g daily to complete 7 days treatment) or no study drug. The primary outcome was the rate of viral clearance (derived under a linear mixed-effects model from the daily log 10 viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 8 days [18 swabs per patient]), assessed in a modified intention-to-treat population (mITT). The safety population included all patients who received at least one dose of the allocated intervention. This ongoing adaptive platform trial was registered at ClinicalTrials.gov (NCT05041907) on 13/09/2021. Results In the final analysis, the mITT population contained data from 114 patients randomised to favipiravir and 126 patients randomised concurrently to no study drug. Under the linear mixed-effects model fitted to all oropharyngeal viral density estimates in the first 8 days from randomisation (4,318 swabs), there was no difference in the rate of viral †
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s12879-023-08835-3. Authors' contributions V.L., J.A.W., S.B., W.H.K.S., and N.J.W wrote the first draft of the manuscript. P.J., V.L., T.S., T.N., B.H., S.S., K.P., P.B., V.C., P.J.A., M.M., S.P., W.P., W.P. were responsible for collection of clinical data. T.N. was responsible for data curation. J.A.W. was responsible for statistical analysis and the figures. S.K., W.M., M.Y.A., R.A.S., F.M.S., R.T., M.I., K.C. were responsible for laboratory testing and analysis. V.K., J.T., were responsible for trial set-up and monitoring. C.C. was responsible for coordination of the study in Brazil and J.J.C. and S.B. for safety monitoring and document preparation. W.R.J.T., A.M.D, N.P.J.D, N.J.W supervised the study and gave scientific input. All authors reviewed the manuscript.
Additional file 1: Supplementary
Availability of data and materials All code and data are openly accessible via GitHub: https:// github. com/ jwato watson/ PLATC OV-Favip iravir. The final datasets will be stored locally and securely at the Mahidol Oxford Research Unit for long-term storage and access. Additional anonymised participant data can be made available by request on a case-by-case basis from the MORU Data Access Committee at datasharing@tropmedres.ac and can be made available by request to the corresponding author.
Declarations Ethics approval and consent to participate
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