Abstract: medRxiv preprint doi: https://doi.org/10.1101/2022.06.06.22275902; this version posted June 8, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 1 Early Treatment of Favipiravir in COVID-19 Patients Without Pneumonia: A Multicentre, 2 Open-Labelled, Randomized Control Study 3 Rujipas Sirijatuphata, Weerawat Manosuthib, Suvimol Niyomnaithamc,d, Andrew Owene, 4 Katherine K. Copelandf, Lantharita Charoenpongb, Manoch Rattanasompattikulg, Surakameth 5 Mahasirimongkolh, Kulkanya Chokephaibulkitd,i* 6 7 a 8 Thailand; bBamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, 9 Thailand; cDepartment of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol 10 University, Thailand; dSiriraj Institute of Clinical Research (SICRES), Mahidol University, 11 Thailand; eInstitute of Systems, Molecular and Integrative Biology, University of Liverpool, 12 United Kingdom; fMahidol University International College, Salaya, Nakhon Pathom, Thailand; 13 g 14 Mahidol University, Thailand; hDivision of Genomic Medicine and Innovation Support, 15 Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; iDepartment 16 of Paediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Medical Department, Golden Jubilee Medical Centre, Faculty of Medicine Siriraj Hospital, 17 18 *Corresponding author: Kulkanya Chokephaibulkit, MD, 19 2 Wanglang Road, Bangkoknoi, Bangkok 10700, Thailand 20 Tel: (+66) 2-4141899; Fax: (+66) 2-4128243, 21 E-mail: kulkanya.cho@mahidol.ac.th. NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2022.06.06.22275902; this version posted June 8, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 22 Abstract 23 We investigated Favipiravir (FPV) efficacy in mild cases of COVID-19 without pneumonia and 24 its effects towards viral clearance, clinical condition, and risk of COVID-19 pneumonia 25 development. PCR-confirmed SARS-CoV-2-infected patients without pneumonia were enrolled 26 (2:1) within 10 days of symptomatic onset into FPV and control arms. The former received 1800 27 mg FPV twice-daily (BID) on Day 1 and 800 mg BID 5-14 days thereafter until negative viral 28 detection, while the latter received supportive care only. The primary endpoint was time to clinical 29 improvement, which was defined by a reduced National Early Warning Score (NEWS) or score of 30 <1. 62 patients (41 female) comprised the FPV arm (median age: 32 years, median BMI: 22 kg/m²) 31 and 31 patients (19 female) comprised the control arm (median age: 28 years, median BMI: 22 32 kg/m². The median time to sustained clinical improvement by NEWS was 2 vs 14 days for FPV 33 and control arms respectively (adjusted hazard ratio (aHR) of 2.77, 95% CI 1.57-4.88, P <0.001). 34 The FPV arm also had significantly higher likelihoods of..