CORIMUNO-19,20Hermine O Mariette X Tharaux PL Resche-Rigon M Porcher R Ravaud P Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia: a randomized clinical trial. published October, 2020 (NCT04331808)Open-label RCT; 1:1 ratioTocilizumab 8 mg/kg versus usual care; option for second dose at 72 hAdults with COVID-19-related moderate, severe, or critical pneumonia requiring O2 ≥3 L/min; patients on non-invasive or invasive mechanical ventilation excluded131 (64 tocilizumab, 67 usual care)Mean of 10 days from symptom onset; median of 1 day from hospitalisationScore >5 on WHO 10-point Clinical Progression Scale at day 4; survival free from mechanical ventilation at day 14Clinical status; overall survival; time to discharge; time to oxygen supply dependencyIndeterminate for primary outcome (median HR 0·58, 90% CrI 0·33–1·00); indeterminate for secondary outcomes17% of patients on steroids; none on remdesivir; not critically illRCT-TCZ-COVID-19,21Salvarani C Dolci G Massari M et al.Effect of tocilizumab vs standard care on clinical worsening in patients hospitalized with COVID-19 pneumonia: a randomized clinical trial. published October, 2020 (NCT04346355)Open-label RCT; 1:1 ratioTocilizumab 8 mg/kg versus standard of care; second dose at 12 hPatients aged ≥18 years with COVID-19 pneumonia, PaO2/FiO2 200–300, and inflammatory phenotype, without mechanical ventilation at baseline; patients admitted to ICU, of advanced age, or with high burden of comorbidities excluded126 (60 tocilizumab, 66 standard of care)Median of 8 days from symptom onset; median of 2 days from hospitalisationClinical worsening at 14 days, including ICU admission, death, or PaO2/FiO2 <150ICU admission; death at 14 and 30 daysIndeterminate for primary outcome (RR 1·05, 0·59–1·86); indeterminate for secondary outcomes<5% of patients on steroids; none on remdesivir; not critically illBACC Bay,22Stone JH Frigault MJ Serling-Boyd NJ et al.Efficacy of tocilizumab in patients hospitalized with Covid-19. published December, 2020 (NCT04356937)Double-blind RCT; 2:1 ratioTocilizumab 8 mg/kg versus placebo; single dosePatients aged 19–85 years with confirmed COVID-19, hyperinflammatory state, and pulmonary infiltrates, fever, or need for supplemental O2; patients with higher risk of infection or O2 >10 L/min excluded243 (161 tocilizumab, 82 placebo)Median of 9 days from symptom onset; within 72 h of worseningMechanical ventilation or deathClinical worsening (ordinal scale)Indeterminate for primary outcome (HR 0·83, 0·38–1·81); indeterminate for secondary outcome10% of patients on steroids; 32% on remdesivir; 4% on HFNOTOCIBRAS,23Veiga VC Prats JAGG Farias DLC et al.Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial. published January, 2021 (NCT04403685)Open-label RCT; 1:1 ratioTocilizumab 8 mg/kg versus standard of care; single doseAdults hospitalised with severe COVID-19 receiving supplemental O2 or mechanical ventilation, with high inflammatory markers; patients with uncontrolled infection, liver disease, or renal disease excluded129 (65 tocilizumab, 64 standard of care)Mean of 10 days from symptom onsetClinical status (ordinal scale) at day 15Death at 28 daysIndeterminate for primary outcome (OR 1·54, 0·66–3·66); indeterminate for secondary outcome71% pf patients on steroids; none on remdesivir; 32% on non-invasive ventilation or HFNO; 16% on invasive mechanical ventilationEMPACTA,24Salama C Han J Yau L et al.Tocilizumab in patients hospitalized with Covid-19 pneumonia. published January, 2021 (NCT04372186)Double-blind RCT; 2:1 ratioTocilizumab 8 mg/kg versus placebo; option for second dose at 8–24 hPatients aged ≥18 years with COVID-19 pneumonia receiving supplemental O2; patients on non-invasive or invasive mechanical ventilation, with active infection, or at risk of imminent death excluded388 (259 tocilizumab, 129 placebo)Median of 8 days from symptoms; median of 1 day from diagnosisMechanical ventilation or death by day 28Median time to hospital discharge; improvement in clinical status (ordinal scale)Positive for primary outcome (HR 0·56, 0·33–0·97); indeterminate for secondary outcomes>80% of patients on steroids; >70% on antivirals; 27% critically ill or on HFNOCOVACTA,25Rosas IO Bräu N Waters M et al.Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. published February, 2021 (NCT04320615)Double-blind RCT; 2:1 ratioTocilizumab 8 mg/kg versus placebo; option for second dose at 8–24 hPatients aged ≥18 years with COVID-19 pneumonia, and SpO2 ≤93% or PaO2/FiO2 <300; patients with active infection or at risk of imminent death excluded452 (301 tocilizumab, 151 placebo)Mean of 12 days from symptom onset; median of 5 days from mechanical ventilationClinical status (7-category ordinal scale) at day 28Death at 28 days; ventilator-free days during 28 daysIndeterminate for primary outcome (between-group difference in median clinical status −1·00, −2·50 to 0·00); indeterminate for secondary outcomes22% of patients on steroids (more in the placebo group); 25% on antivirals; 37% on invasive mechanical ventilationREMAP-CAP,26The REMAP-CAP Investigators
Interleukin-6 receptor antagonists in critically ill patients with Covid-19. published February, 2021 (NCT02735707)Open-label RCT (adaptive platform trial); balanced assignment (ratio dependent on number of interventions available at each site)Tocilizumab 8 mg/kg or sarilumab 400 mg versus standard of care; option for second dose of tocilizumab at 12–24 hCritically ill patients aged ≥18 years receiving respiratory or cardiovascular organ support, enrolled within 24 h of ICU admission; patients at risk of imminent death excluded865 (353 tocilizumab, 48 sarilumab, 402 standard of care)Median of 1 day from hospital admission to randomisation; median of 14 h from ICU admissionOrgan support-free days or death up to 21 daysIn hospital or death at 90 days; time to ICU discharge; time to hospital dischargePositive for primary outcome (tocilizumab OR 1·64, 95% Crl 1·25–2·14; sarilumab 1.76, 1·17–2·91); positive for secondary outcomes>80% of patients on steroids; 33% on remdesivir; 29% on HFNO; 42% on non-invasive ventilation; 29% on invasive mechanical ventilationRECOVERY,27Horby PW Pessoa-Amorim G Peto L et al.Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): preliminary results of a randomised, controlled, open-label, platform trial. preprint published February, 2021 (NCT04381936)Open-label RCT (platform trial); 1:1 ratioTocilizumab 8 mg/kg versus usual care; option for second dose at 12–24 hPatients aged ≥18 years with severe COVID-19, with SpO2 <92% on air or requiring O2 therapy, and C-reactive protein ≥75 mg/L; patients with active infection excluded4116 (2022 tocilizumab, 2094 usual care)Median of 10 days from symptom onset; median of 2 days from hospitalisationAll-cause death at 28 daysTime to hospital discharge; invasive mechanical ventilation or death at 28 daysPositive for primary outcome (RR 0·86, 0·77–0·96); positive for secondary outcomes>80% of patients on steroids; 22% on remdesivir; 41% on non-invasive ventilation or HFNO; 14% on invasive mechanical ventilationCOVINTOC,28Soin AS Kumar K Choudhary NS et al.Tocilizumab plus standard care versus standard care in patients in India with moderate to severe COVID-19-associated cytokine release syndrome (COVINTOC): an open-label, multicentre, randomised, controlled, phase 3 trial. published March, 2021 (CTRI/2020/05/025369)Open-label RCT; 1:1 ratioTocilizumab 6 mg/kg versus standard of care; option for second dose at 12 h to 7 daysPatients aged ≥18 years admitted to hospital with moderate (respiratory rate 15–30 per min, SpO2 90–94%) to severe (respiratory rate ≥30 per min, SpO2 <90%, or ARDS or septic shock) COVID-19; patients with active infection or at risk of imminent death excluded180 (90 tocilizumab, 90 standard of care)Not reportedProgression of COVID-19 from moderate to severe or from severe to death up to day 14Time to clinical improvement; proportion of patients with improvement in ASTCT CRS gradeIndeterminate for primary outcome (mean difference −3·7, −18·2 to 11·2); indeterminate for secondary outcomes91% of patients on steroids; 42% on remdesivir; 27% on non-invasive ventilation; 5% on invasive mechanical ventilationLescure et al,29Lescure F-X Honda H Fowler RA et al.Sarilumab treatment of hospitalised patients with severe or critical COVID-19: a multinational, randomised, adaptive, phase 3, double-blind, placebo-controlled trial. published March, 2021 (NCT04327388)Double-blind RCT (adaptive trial); 2:2:1 ratioSarilumab 400 mg or sarilumab 200 mg versus placebo; option for second dose at 24–48 hPatients aged ≥18 years admitted to hospital with severe COVID-19 pneumonia or with critical disease requiring supplemental O2 or ICU admission; patients with active infection, dysfunction of ≥2 organ systems, on renal replacement therapy or extracorporeal support, or at risk of imminent death excluded420 (173 sarilumab 400 mg, 161 sarilumab 200 mg, 86 placebo)Median of 5 days from dyspnoea onset; median of 3 days from hospitalisationTime to clinical improvement (2 or more points on 7-point ordinal scale)Death at 28 daysIndeterminate for primary outcome sarilumab 400 mg HR 1·14, 0·84–1·54; sarilumab 200 mg 1·03, 0·75–1·40; indeterminate for secondary outcomes20% of patients on steroids; <1% on remdesivir; 6% on HFNO; 2% on non-invasive ventilation; 12% on invasive mechanical ventilation