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Randomized Controlled Trial
. 2024 Jan 15;24(1):89.
doi: 10.1186/s12879-023-08835-3.

Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial

Viravarn Luvira  1 , William H K Schilling #  2   3 , Podjanee Jittamala #  4   5 , James A Watson  4   6 , Simon Boyd  4   6 , Tanaya Siripoon  1 , Thundon Ngamprasertchai  1 , Pedro J Almeida  7 , Maneerat Ekkapongpisit  4 , Cintia Cruz  4   6 , James J Callery  4   6 , Shivani Singh  4 , Runch Tuntipaiboontana  4 , Varaporn Kruabkontho  4 , Thatsanun Ngernseng  4 , Jaruwan Tubprasert  4 , Mohammad Yazid Abdad  4   6 , Srisuda Keayarsa  1 , Wanassanan Madmanee  4 , Renato S Aguiar  8 , Franciele M Santos  8 , Pongtorn Hanboonkunupakarn  9 , Borimas Hanboonkunupakarn  1   4 , Kittiyod Poovorawan  1   4 , Mallika Imwong  4   10 , Walter R J Taylor  1   4 , Vasin Chotivanich  11 , Kesinee Chotivanich  1   4 , Sasithon Pukrittayakamee  1   4 , Arjen M Dondorp  4   6 , Nicholas P J Day  4   6 , Mauro M Teixeira  7 , Watcharapong Piyaphanee  1 , Weerapong Phumratanaprapin  1 , Nicholas J White  12   13 ; PLATCOV Collaborative Group
Affiliations
Randomized Controlled Trial

Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial

Viravarn Luvira et al. BMC Infect Dis. .

Abstract

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 log10 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 clearance between patients given favipiravir and patients receiving no study drug; a -1% (95% credible interval: -14 to 14%) difference. High dose favipiravir was well-tolerated.

Interpretation: Favipiravir does not accelerate viral clearance in early symptomatic COVID-19. The viral clearance rate estimated from quantitative measurements of oropharyngeal eluate viral densities assesses the antiviral efficacy of drugs in vivo with comparatively few studied patients.

Keywords: Antiviral efficacy; COVID-19; Early treatment; Favipiravir; Pharmacometrics; SARS-CoV-2.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
CONSORT diagram
Fig. 2
Fig. 2
a (left): qPCR estimates of oropharyngeal swab eluate viral densities (all measurements) with the daily median values graphed by treatment arm (green: no study drug; brown: favipiravir). b (right): Estimated change in the rate of viral clearance under the linear (red) and non-linear (blue) models (median posterior estimates and corresponding 80% (thick line) and 95% (thin line) credible intervals are shown)
Fig. 3
Fig. 3
a (left): Estimated viral clearance half-lives ordered by increasing median estimate (lines show 80% credible intervals). b (right): Relationship between body weight and median estimated viral clearance half-life. As the individual doses were all the same, body weight is a surrogate for dose/kg and thus exposure
See this image and copyright information in PMC

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