Early treatment of Favipiravir in COVID-19 patients without pneumonia: a multicentre, open-labelled, randomized control study

ABSTRACT

We investigated Favipiravir (FPV) efficacy in mild cases of COVID-19 without pneumonia and its effects towards viral clearance, clinical condition, and risk of COVID-19 pneumonia development. PCR-confirmed SARS-CoV-2-infected patients without pneumonia were enrolled (2:1) within 10 days of symptomatic onset into FPV and control arms. The former received 1800 mg FPV twice-daily (BID) on Day 1 and 800 mg BID 5–14 days thereafter until negative viral detection, while the latter received only supportive care. The primary endpoint was time to clinical improvement, defined by a National Early Warning Score (NEWS) of ≤1. 62 patients (41 female) comprised the FPV arm (median age: 32 years, median BMI: 22 kg/m²) and 31 patients (19 female) comprised the control arm (median age: 28 years, median BMI: 22 kg/m²). The median time to sustained clinical improvement, by NEWS, was 2 and 14 days for FPV and control arms, respectively (adjusted hazard ratio (aHR) of 2.77, 95% CI 1.57–4.88, P < .001). The FPV arm also had significantly higher likelihoods of clinical improvement within 14 days after enrolment by NEWS (79% vs. 32% respectively, P < .001). 8 (12.9%) and 7 (22.6%) patients in FPV and control arms developed mild pneumonia at a median (range) of 6.5 (1–13) and 7 (1–13) days after treatment, respectively (P = .316). All recovered well without complications. We can conclude that early treatment of FPV in symptomatic COVID-19 patients without pneumonia was associated with faster clinical improvement.

Trial registration: Thai Clinical Trials Registry identifier: TCTR20200514001.

KEYWORDS:

• COVID-19
• Favipiravir
• Thailand
• antiviral
• RdRp inhibitor

Acknowledgements

This study was developed in collaboration of Faculty of Medicine Siriraj Hospital, Mahidol University and National Centre for Global Health and Medicine, Japan. The study drug (Favipiravir) was supported by FUJIFILM Toyama Chemical Co., Ltd. We would like to thank all the staff in the three participating hospitals who provided support for this study.

Disclosure statement

AO is a Director of Tandem Nano Ltd. and co-inventor of patents relating to drug delivery. AO has received research funding from ViiV Healthcare, Merck, and Janssen and consultancy from Gilead, ViiV, and Merck not related to COVID-19 or the current work. Other authors have none to declare.

Additional information

Funding

This work was supported by the National Research Council of Thailand under grant (63-088); and the Siriraj Research and Development Fund, Faculty of Medicine Siriraj Hospital, Mahidol University under grant (IO: R016434001). AO acknowledges funding from Unitaid for project LONGEVITY, Wellcome Trust under grant (222489/Z/21/Z); EPSRC under grant (EP/R024804/1; EP/S012265/1); and NIH under grant (R01AI134091; R24 AI118397).