Tocilizumab, sarilumab and anakinra in critically ill patients with COVID-19: a randomised, controlled, open-label, adaptive platform trial
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: INTRODUCTION: Tocilizumab improves outcomes in critically ill patients with COVID-19. Whether other immune-modulator strategies are equally effective or better is unknown. METHODS: We investigated treatment with tocilizumab, sarilumab, anakinra and no immune modulator in these patients. In this ongoing, adaptive platform trial in 133 sites in 9 countries, we randomly assigned patients with allocation ratios dependent on the number of interventions available at each site. The primary outcome was an ordinal scale combining in-hospital mortality (assigned -1) and days free of organ support to day 21 in survivors. The trial used a Bayesian statistical model with predefined triggers for superiority, inferiority, efficacy, equivalence or futility. RESULTS: Of 2274 critically ill participants enrolled between 25 March 2020 and 10 April 2021, 972 were assigned to tocilizumab, 485 to sarilumab, 378 to anakinra and 418 to control. Median organ support-free days were 7 (IQR -1, 16), 9 (IQR -1, 17), 0 (IQR -1, 15) and 0 (IQR -1, 15) for tocilizumab, sarilumab, anakinra and control, respectively. Median adjusted ORs were 1.46 (95% credible intervals (CrI) 1.13, 1.87), 1.50 (95% CrI 1.13, 2.00) and 0.99 (95% CrI 0.74, 1.35) for tocilizumab, sarilumab and anakinra relative to control, yielding 99.8%, 99.8% and 46.6% posterior probabilities of superiority, respectively, compared with control. All treatments appeared safe. CONCLUSIONS: In critically ill patients with COVID-19, tocilizumab and sarilumab have equivalent effectiveness at reducing duration of organ support and death. Anakinra is not effective in this population. TRIAL REGISTRATION NUMBER: NCT02735707.
Source: Thorax
Authors: Lennie Derde, Anthony C Gordon, Paul R Mouncey, Farah Al-Beidh, Kathryn M Rowan, Alistair D Nichol, Yaseen M Arabi, Djillali Annane, Abigail Beane, Richard Beasley, Marc J M Bonten, Charlotte A Bradbury, Frank M Brunkhorst, Adrian Buzgau, Meredith Buxton, Allen C Cheng, Nicola Cooper, Matthew Cove, Olaf L Cremer, Michelle A Detry, Eamon J Duffy, Lise J Estcourt, Mark Fitzgerald, James Galea, Herman Goossens, Rashan Haniffa, Thomas E Hills, David T Huang, Nao Ichihara, Andrew King, Fran�ois Lamontagne, Patrick R Lawler, Helen L Leavis, Roger J Lewis, Edward Litton, John C Marshall, Florian B Mayr, Daniel F McAuley, Anna McGlothlin, Shay P McGuinness, Bryan J McVerry, Susan C Morpeth, Srinivas Murthy, Mihai G Netea, Kayode Ogungbenro, Katrina Orr, Rachael L Parke, Jane C Parker, Asad E Patanwala, Ville Pettila, Luis Felipe Reyes, Hiroki Saito, Marlene S Santos, Christina T Saunders, Christopher W Seymour, Manu Shankar-Hari, Wendy I Sligl, Alexis F Turgeon, Anne M Turner, Steven Y C Tong, Suvi Vaara, Taryn Youngstein, Ryan Zarychanski, Cameron Green, Alisa M Higgins, Colin J McArthur, Lindsay R Berry, Elizabeth Lorenzi, Scott Berry, Steve A Webb, Derek C Angus, Frank L van de Veerdonk
Institutions: University Medical Center Utrecht, Imperial College London, Intensive Care National Audit & Research Centre, University College Dublin, King Saud bin Abdulaziz University for Health Sciences, Université de Versailles Saint-Quentin-en-Yvelines, Hôpital Raymond-Poincaré, University of Oxford, Mahidol Oxford Tropical Medicine Research Unit, Medical Research Institute of New Zealand, University of Bristol, Jena University Hospital, Monash University, The Alfred Hospital, National University of Singapore, Berry Consultants, LLC (United States), Auckland City Hospital, University of Antwerp, University of Pittsburgh, The University of Tokyo, Université de Sherbrooke, McGill University, The University of Western Australia, University of Toronto, University of Pittsburgh Medical Center, Queen's University Belfast, Royal Prince Alfred Hospital, UPMC Health System, Middlemore Hospital, University of British Columbia, Radboud University Medical Center, University of Manchester, Fiona Stanley Hospital, University of Auckland, University of Helsinki, Universidad de La Sabana, St. Marianna University School of Medicine, Unity Health Toronto, Centre for Inflammation Research, University of Edinburgh, University of Alberta, Université Laval, Peter Doherty Institute, University of Manitoba
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Sanofi, Wellcome Trust, Translational Breast Cancer Research Consortium, National Institute for Health and Care Research, Department of Health and Social Care, European Commission, ZonMw, Université Pierre et Marie Curie, National University Health System, Swedish Orphan Biovitrum, Minderoo Foundation, Canadian Institutes of Health Research, Medical Research Council, National Health and Medical Research Council, National Medical Research Council, Health Research Council of New Zealand, NIHR Imperial Biomedical Research Centre, FP7 Health
Awards: Platform foR European Preparedness Against (Re-)emerging Epidemics, G1682509464, European Clinical Research Alliance on Infectious Diseases, G2306515209, G259677009, Viral strategies to prevent host cell death, G4367458895, G4659202922, Rapid European SARS-CoV-2 Emergency research Response, G5068291530, Implementing an innovative electronic registry in a new regional intensive care network to improve quality of care and establish a platform for clinical trials in resource-limited settings in Asia, G5918494183, Improving health care burden amongst sepsis survivors by reducing infection-related rehospitalisation, G6961869428, G7447711091, G7775121457
OpenAlex ID: W4410382863