Evaluation of the effectiveness of remdesivir in treating severe COVID-19 using data from the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, national cohort study

Abstract: medRxiv preprint doi: https://doi.org/10.1101/2021.06.18.21259072; this version posted June 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.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 . Evaluation of the effectiveness of remdesivir in treating severe COVID-19 using data from the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, national cohort study. Short Running title: ISARIC4C Remdesivir effectiveness study Authors Arch BN1, Kovacs D2*, Scott JT3*, Jones AP1, Harrison EM4, Rosala-Hallas A1, Gamble CG1, Openshaw PJM 5, Baillie JK6, Semple MG7,8 on behalf of ISARIC4C Investigators *Joint 2nd authors Affiliations 1. Liverpool Clinical Trials Centre, Clinical Directorate, Faculty of Health and Life Sciences, University of Liverpool, UK. 2. Institute of Biodiversity, Animal health and Comparative Medicine, University of Glasgow, Glasgow, UK 3. MRC-University of Glasgow Centre for Virus Research, Glasgow, UK 4. Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK 5. National Heart and Lung Institute, Imperial College London, London, UK 6. Roslin Institute, University of Edinburgh, Edinburgh, UK 7. Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK. 8. Department of Respiratory Medicine, Alder Hey Children’s Hospital, Liverpool, UK. Corresponding author Barbara Arch. Liverpool Clinical Trials Centre, University of Liverpool, Institute in the Park, Alder Hey Childrens Hospital, Eaton Road, Liverpool, L12 2AP. Email: barbara.arch@liverpool.ac.uk, Tel: +44(0)151 795 8751 Word Count Abstract 267/300 Manuscript (excluding Research in Context Panel) 3,579/3,500 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. Page 1 of 22 medRxiv preprint doi: https://doi.org/10.1101/2021.06.18.21259072; this version posted June 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.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 . Abstract Background Remdesivir was given UK early-access approval for use in COVID-19 in people aged 12 years and older on 26th May 2020 on the basis of unmet clinical need. Evidence on the side effects, complications of therapy and effectiveness of this therapy is lacking or conflicting. Methods Adults with severe COVID-19 treated with remdesivir were compared with propensity-score matched controls, identified from the ISARIC WHO Clinical Characterisation Protocol study of UK hospitalised patients with COVID-19. Remdesivir patients were matched to controls according to baseline underlying 14-day mortality risk. The effect of remdesivir on short-term outcomes was investigated (primary outcome: 14-day mortality). Effect sizes were estimated and adjusted for potential confounders using multivariable modelling. Results 1,549 patients given remdesivir and 4,964 matched controls were identified satisfying inclusion and exclusion criteria. The balance diagnostic threshold was achieved. Patients had symptoms for a median of 6 days prior to..