Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open- label, randomised, controlled adaptive platform trial
Viravarn Luvira, William Hk 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 Rj Taylor, Vasin Chotivanich, Kesinee Chotivanich, Sasithon Pukrittayakamee, Arjen M Dondorp, Nicholas Pj Day, Mauro M Teixeira, Watcharapong Piyaphanee, Weerapong Phumratanaprapin, Nicholas J White
doi:10.21203/rs.3.rs-2675703/v1
Background: Favipiravir, an anti-in uenza 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 assessed in a modi ed intention-to-treat population (mITT) 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]). The safety population included all patients who received at least one dose of the allocated intervention. This ongoing adaptive platform trial is registered at ClinicalTrials.gov (NCT05041907).
Results: In the nal 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 tted to all oropharyngeal viral density estimates in the rst 8 days from randomisation (4,318 swabs), there was no difference in the rate of viral clearance between patients administered favipiravir and patients receiving no study drug -1% (95% CI: -14 to 14% change). High dose favipiravir was well tolerated.
Interpretation: Favipiravir does not accelerate viral clearance in early symptomatic COVID-19.
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SupplementaryMaterialsFavipiravirBMC.docx
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