1. Namilumab or infliximab compared with standard of care in hospitalised patients with COVID-19 (CATALYST): a randomised, multicentre, multi-arm, multistage, open-label, adaptive, phase 2, proof-of-concept trial
- Author
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Benjamin A Fisher, Tonny Veenith, Daniel Slade, Charlotte Gaskell, Matthew Rowland, Tony Whitehouse, James Scriven, Dhruv Parekh, Madhu S Balasubramaniam, Graham Cooke, Nick Morley, Zoe Gabriel, Matthew P Wise, Joanna Porter, Helen McShane, Ling-Pei Ho, Philip N Newsome, Anna Rowe, Rowena Sharpe, David R Thickett, Julian Bion, Simon Gates, Duncan Richards, Pamela Kearns, Bryan Williams, Rebecca Turner, Vincenzo Libri, Francis Mussai, Gary Middleton, Sarah Bowden, Mansoor Bangash, Fang Gao-Smith, Jaimin Patel, Elizabeth Sapey, Mark Thomas, Mark Coles, Peter Watkinson, Naj Rahman, Brian Angus, Alexander J. Mentzer, Alex Novak, Marc Feldman, Alex Richter, Sian Faustini, Camilla Bathurst, Joseph Van de Wiel, Susie Mee, Karen James, Bushra Rahman, Karen Turner, Adam Hill, Anthony Gordon, Christina Yap, Michael Matthay, Danny McAuley, Andrew Hall, Paul Dark, Andrew McMichael, Investigators, CATALYST, National Institute for Health Research, UK Research and Innovation, and NIHR
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PNEUMONIA ,Pulmonary and Respiratory Medicine ,Adolescent ,BLOCKADE ,Respiratory System ,Antibodies, Monoclonal, Humanized ,COVID-19/drug therapy ,1117 Public Health and Health Services ,Critical Care Medicine ,General & Internal Medicine ,Humans ,TUMOR-NECROSIS-FACTOR ,Science & Technology ,SARS-CoV-2 ,COVID-19 ,CATALYST investigators ,1103 Clinical Sciences ,Bayes Theorem ,Standard of Care ,Articles ,COLONY-STIMULATING FACTOR ,Infliximab ,COVID-19 Drug Treatment ,Infliximab/therapeutic use ,Treatment Outcome ,Life Sciences & Biomedicine ,1199 Other Medical and Health Sciences - Abstract
Background: Dysregulated inflammation is associated with poor outcomes in COVID-19. We aimed to assess the efficacy of namilumab (a granulocyte-macrophage colony stimulating factor inhibitor) and infliximab (a tumour necrosis factor inhibitor) in hospitalised patients with COVID-19, to prioritise agents for phase 3 trials. Methods: In this randomised, multicentre, multi-arm, multistage, parallel-group, open-label, adaptive, phase 2, proof-of-concept trial (CATALYST), we recruited patients (aged ≥16 years) admitted to hospital with COVID-19 pneumonia and C-reactive protein (CRP) concentrations of 40 mg/L or greater, at nine hospitals in the UK. Participants were randomly assigned with equal probability to usual care or usual care plus a single intravenous dose of namilumab (150 mg) or infliximab (5 mg/kg). Randomisation was stratified by care location within the hospital (ward vs intensive care unit [ICU]). Patients and investigators were not masked to treatment allocation. The primary endpoint was improvement in inflammation, measured by CRP concentration over time, analysed using Bayesian multilevel models. This trial is now complete and is registered with ISRCTN, 40580903. Findings: Between June 15, 2020, and Feb 18, 2021, we screened 299 patients and 146 were enrolled and randomly assigned to usual care (n=54), namilumab (n=57), or infliximab (n=35). For the primary outcome, 45 patients in the usual care group were compared with 52 in the namilumab group, and 29 in the usual care group were compared with 28 in the infliximab group. The probabilities that the interventions were superior to usual care alone in reducing CRP concentration over time were 97% for namilumab and 15% for infliximab; the point estimates for treatment–time interactions were –0·09 (95% CI –0·19 to 0·00) for namilumab and 0·06 (–0·05 to 0·17) for infliximab. 134 adverse events occurred in 30 (55%) of 55 patients in the namilumab group compared with 145 in 29 (54%) of 54 in the usual care group. 102 adverse events occurred in 20 (69%) of 29 patients in the infliximab group compared with 112 in 17 (50%) of 34 in the usual care group. Death occurred in six (11%) patients in the namilumab group compared with ten (19%) in the usual care group, and in four (14%) in the infliximab group compared with five (15%) in the usual care group. Interpretation: Namilumab, but not infliximab, showed proof-of-concept evidence for reduction in inflammation—as measured by CRP concentration—in hospitalised patients with COVID-19 pneumonia. Namilumab should be prioritised for further investigation in COVID-19.
- Published
- 2022
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