• Carlo Salvarani, Giovanni Dolci, Marco Massari, Domenico Franco Merlo, Silvio Cavuto, Luisa Savoldi, Paolo Bruzzi, Fabrizio Boni, Luca Braglia, Caterina Turrà, Pier Ferruccio Ballerini, Roberto Sciascia, Lorenzo Zammarchi, Ombretta Para, Pier Giorgio Scotton, Walter Omar Inojosa, Viviana Ravagnani, Nicola Duccio Salerno, Pier Paolo Sainaghi, Alessandro Brignone, Mauro Codeluppi, Elisabetta Teopompi, Maurizio Milesi, Perla Bertomoro, Norbiato Claudio, Mario Salio, Marco Falcone, Giovanni Cenderello, Lorenzo Donghi, Valerio Del Bono, Paolo Luigi Colombelli, Andrea Angheben, Angelina Passaro, Giovanni Secondo, Renato Pascale, Ilaria Piazza, Nicola Facciolongo, Massimo Costantini, and RCT-TCZ-COVID-19 Study Group.
• SOC Reumatologia, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
• JAMA Intern Med. 2021 Jan 1; 181 (1): 24-31.

ImportanceThe coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile.ObjectiveTo evaluate the effect of early tocilizumab administration vs standard therapy in preventing clinical worsening in patients hospitalized with COVID-19 pneumonia.Design, Setting, And ParticipantsProspective, open-label, randomized clinical trial that randomized patients hospitalized between March 31 and June 11, 2020, with COVID-19 pneumonia to receive tocilizumab or standard of care in 24 hospitals in Italy. Cases of COVID-19 were confirmed by polymerase chain reaction method with nasopharyngeal swab. Eligibility criteria included COVID-19 pneumonia documented by radiologic imaging, partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2/Fio2) ratio between 200 and 300 mm Hg, and an inflammatory phenotype defined by fever and elevated C-reactive protein.InterventionsPatients in the experimental arm received intravenous tocilizumab within 8 hours from randomization (8 mg/kg up to a maximum of 800 mg), followed by a second dose after 12 hours. Patients in the control arm received supportive care following the protocols of each clinical center until clinical worsening and then could receive tocilizumab as a rescue therapy.Main Outcome And MeasuresThe primary composite outcome was defined as entry into the intensive care unit with invasive mechanical ventilation, death from all causes, or clinical aggravation documented by the finding of a Pao2/Fio2 ratio less than 150 mm Hg, whichever came first.ResultsA total of 126 patients were randomized (60 to the tocilizumab group; 66 to the control group). The median (interquartile range) age was 60.0 (53.0-72.0) years, and the majority of patients were male (77 of 126, 61.1%). Three patients withdrew from the study, leaving 123 patients available for the intention-to-treat analyses. Seventeen patients of 60 (28.3%) in the tocilizumab arm and 17 of 63 (27.0%) in the standard care group showed clinical worsening within 14 days since randomization (rate ratio, 1.05; 95% CI, 0.59-1.86). Two patients in the experimental group and 1 in the control group died before 30 days from randomization, and 6 and 5 patients were intubated in the 2 groups, respectively. The trial was prematurely interrupted after an interim analysis for futility.Conclusions And RelevanceIn this randomized clinical trial of hospitalized adult patients with COVID-19 pneumonia and Pao2/Fio2 ratio between 200 and 300 mm Hg who received tocilizumab, no benefit on disease progression was observed compared with standard care. Further blinded, placebo-controlled randomized clinical trials are needed to confirm the results and to evaluate possible applications of tocilizumab in different stages of the disease.Trial RegistrationClinicalTrials.gov Identifier: NCT04346355; EudraCT Identifier: 2020-001386-37.

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