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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ObjectiveQuantify the efficacy of strategies to prevent contrast-induced acute kidney injury (CI-AKI) in high-risk patients undergoing coronary angiography (CAG) with or without percutaneous coronary intervention (PCI).BackgroundCI-AKI remains a common problem. The renoprotective efficacy of existing pharmacological agents remains uncertain in high-risk populations.MethodsSystematic review and meta-analysis of randomised controlled trials (RCTs) to compare different strategies versus hydration in patients with chronic kidney disease (CKD) undergoing CAG±PCI. Primary outcome was incident CI-AKI. Fixed-effects meta-analyses estimated ORs, 95% CIs and heterogeneity.ResultsForty-eight RCTs were included. Seven pharmacological strategies were evaluated by multiple RCTs and 10 by one RCT each. These had varying risk of bias; >25% of trials were at high risk of performance bias. Five strategies significantly reduced the odds of CI-AKI: N-acetylcysteine (NAC) (27 trials, 5694 participants; OR=0.77, 95% CI 0.65 to 0.91, p=0.002, I2=36%), ascorbic acid (four trials, 759 participants; OR=0.59, 95% CI 0.39 to 0.89, p=0.01, I2=0%), statin (two trials, 3234 participants; OR=0.59, 95% CI 0.39 to 0.89, p=0.75, I2=0%), trimetazidine (two trials, 214 participants; OR=0.27, 95% CI 0.10 to 0.71, p=0.01, I2=0%) and nicorandil (two trials, 389 participants; OR=0.47, 95% CI 0.23 to 0.94, p=0.03, I2=52%). Theophylline had a similar, but non-significant, effect. A subgroup analysis found that the benefit of NAC was highest in patients requiring a high-contrast dose.ConclusionsSeveral drugs are renoprotective in patients with CKD undergoing CAG±PCI. The evidence is strongest for NAC. We recommend that NAC should be used when a high dose of contrast is anticipated.Trial registration numberPROSPERO registration CRD42014014704.Open Science Framework link: https://osf.io/vxg7d/?view_only=62bad0404b18405abd39ff2ead2575a8