Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Abstract

Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

Tocilizumab in Hospitalized Patients with COVID-19: A Meta Analysis of Randomized Controlled Trials

“…Figure 1 shows the PRISMA flow chart summarizing the search strategy. The literature search identified 38 full-text articles, of which nine RCTs were eligible for inclusion in this study after full read [ 24 – 29 , 31 , 33 ]. A total of 6490 patients were included, of which 3358 patients received tocilizumab, and 3132 received standard care/placebo.…”

“…Concealment of allocation was not mentioned in six trials and therefore risk of allocation concealment remains high in these trials [ 27 – 29 , 31 , 33 , 34 ]. Also, six trials had open-label study design [ 27 – 29 , 31 , 33 , 34 ]. The risk of performance and selection bias was high in these trials as participants and personnel were not blinded to the assigned treatment.…”

“…Risk of attrition bias was deemed high in one trial due to incomplete outcome [ 29 ]. In the rest of the studies, risk of attrition bias was low [ 24 – 28 , 31 , 33 , 34 ].

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“…All nine RCTs reported the outcome of all-cause mortality [ 24 – 29 , 31 , 33 , 34 ]. A total of 846 deaths out of 3358 participants were reported in the tocilizumab arm compared to 943 deaths out of 3132 participants in the standard care or placebo arm.…”

“…Eight RCTs reported the outcome of progression to mechanical ventilation [ 24 , 25 , 27 – 29 , 31 , 33 , 34 ]. 440 out of 2622 participants progressed to mechanical ventilation in the tocilizumab group compared to 536 out of 2526 participants in the other group.…”