Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.
Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.
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DOI：
10.1016/s0140-6736(21)00676-0
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发表时间：
2021-05-01
期刊：
影响因子：
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通讯作者：
RECOVERY Collaborative Group
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文献类型：
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作者：
RECOVERY Collaborative Group
在这项研究中，我们的目的是评估托珠单抗在患有COVID-19的住院成人患者中的作用，这些患者同时患有缺氧和全身性炎症。这项随机、对照、开放标签、平台试验（COVID-19治疗的随机评价[RECOVERY]）正在评估英国因COVID-19住院患者的几种可能治疗方法。缺氧（空气中氧饱和度<92%或需要氧疗）和全身炎症证据（C-反应蛋白≥75 mg/L）的试验参与者有资格以1：1的比例随机分配至单独常规标准治疗组与常规标准治疗+托珠单抗400 mg-800 mg（取决于体重）静脉给药组。如果患者的病情没有改善，可以在12-24小时后给予第二剂。主要结局是在意向治疗人群中评估的28天死亡率。该试验已在ISRCTN（50189673）和ClinicalTrials.gov（NCT 04381936）注册。在2020年4月23日至2021年1月24日期间，招募到RECOVERY试验的21550名患者中的4116名成人被纳入托珠单抗评估，其中包括3385名（82%）接受全身性皮质类固醇的患者。 总体而言，2022例接受托珠单抗治疗的患者中有621例（31%）在28天内死亡，2094例接受常规治疗的患者中有729例（35%）在28天内死亡（率比0.85; 95%CI 0.76 - 0.94; p= 0.0028）。在所有预先指定的患者亚组中观察到一致的结果，包括接受全身性皮质类固醇的患者。托珠单抗组患者在28天内出院的可能性更大（57% vs 50%;率比1.22; 1.12 - 1.33; p<0.0001）。在基线时未接受有创机械通气的患者中，分配托珠单抗的患者达到有创机械通气或死亡复合终点的可能性较低（35% vs 42%;风险比0.84; 95%CI 0.77 - 0.92; p<0.0001）。在患有缺氧和全身性炎症的COVID-19住院患者中，托珠单抗改善了生存率和其他临床结局。无论呼吸支持的量如何，这些益处都是全身性皮质类固醇益处的补充。英国研究和创新（医学研究理事会）和国家健康研究所。
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. 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). 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). 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. UK Research and Innovation (Medical Research Council) and National Institute of Health Research.