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

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

Luvira et al., Research Square, doi:10.21203/rs.3.rs-2675703/v1, PLATCOV, NCT05041907 (history)

Luvira et al., Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open- label, randomised, controlled.., Research Square, doi:10.21203/rs.3.rs-2675703/v1, PLATCOV, NCT05041907

Apr 2023 Source PDF

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High conflict of interest RCT with very low risk patients, high existing immunity, and a post-hoc change to exclude patients more likely to benefit. There was no significant difference in viral clearance with favipiravir among patients with high viral load at baseline. Patients in both arms had very short viral clearance half-life times.

With rapid viral clearance and very low risk patients, infection is less likely to spread to other tissues. Systemic treatment is less applicable, and has less time to reach therapeutic concentrations before self-recovery.

Treatment administered directly to the respiratory tract, e.g. as in [Yildiz Pekoz], may be more effective for COVID-19 in general, and extend applicability to fast-resolving cases with infection primarily localized to the respiratory tract.

Authors note that "all-cause hospitalisation for clinical deterioration (until day 28) was a secondary endpoint", but do not provide the result.

For more discussion of the post-hoc change and other issues see [Schilling].

1. Schilling et al., eLife, doi:10.7554/eLife.83201 (preprint 7/19/2022), Pharmacometrics of high dose ivermectin in early COVID-19: an open label, randomized, controlled adaptive platform trial (PLATCOV), https://elifesciences.org/articles/83201.

2. Yildiz Pekoz et al., Drug Delivery, doi:10.1080/10717544.2022.2118398, Pulmonary delivery of favipiravir inhalation solution for COVID-19 treatment: in vitro characterization, stability, in vitro cytotoxicity, and antiviral activity using real time cell analysis, https://www.tandfonline.com/doi/full/10.1080/10717544.2022.2118398.

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relative clearance rate, 5.7% worse, RR 1.06, p = 0.81, treatment median 16.6 IQR 41.3 n=116, control median 15.7 IQR 38.7 n=132, primary outcome.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Luvira et al., 5 Apr 2023, Randomized Controlled Trial, multiple countries, peer-reviewed, median age 30.1, 35 authors, study period 30 September, 2021 - 31 October, 2022, trial NCT05041907 (history) (PLATCOV).

Contact: william@tropmedres.ac, nickw@tropmedres.ac.

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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.

This is a list of supplementary les associated with this preprint. Click to download. SupplementaryMaterialsFavipiravirBMC.docx

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