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.

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BackgroundScaphoid fractures account for 90% of carpal fractures and occur predominantly in young men. Immediate surgical fixation of this fracture has increased, in spite of insufficient evidence of improved outcomes over non-surgical management. We compared the clinical effectiveness of surgical fixation with cast immobilization and early fixation of those that fail to unite, for ≤2 mm displaced scaphoid waist fractures in adults. MethodsThis pragmatic, multicentre, open-label, parallel-group, two-arm randomised clinical trial included adults who presented to orthopaedic departments of 31 hospitals in England and Wales with a clear, bicortical fracture of the scaphoid waist on radiographs. Participants were randomly assigned to early surgical fixation or below-elbow cast immobilization followed by immediate fixation of confirmed non-union. The primary outcome was the Patient Rated Wrist Evaluation (PRWE) total score at 52 weeks post-randomisation. Registration ISRCTN67901257. FindingsOf 439 randomised patients (mean age 33 years, 363 [83%] men), 408 (93%) were included in the primary analyses. There was no difference in PRWE score at 52 weeks (adjusted mean difference -2•1 points, 95% CI -5•8 to 1•6, p=0•27). There were no differences at 52 weeks for the PRWE pain or function subscales. More participants in the surgery group experienced a surgery-related potentially serious complication than in the cast group (n=31, 14% vs n=3, 1%), but fewer had cast-related complications (n=5, 2% vs n=40, 18%). The number experiencing a medical complication (n=4, 2% vs n=5, 2%) was similar in the two groups." InterpretationAdult patients with ≤2 mm displaced scaphoid waist fracture should have initial cast immobilization and suspected non-unions confirmed and immediately fixed. This will help avoid risks of surgery and mostly limit its use to fixing non-union.