BP-A Beneficência Portuguesa de São Paulo, Rua Maestro Cardim, 769-Bela Vista, São Paulo-SP, 01323-001, Brazil
Brazilian Research in Intensive Care Network-BRICNet, São Paulo, Brazil.
BMJ. 2021 Jan 20;372:n84. doi: 10.1136/bmj.n84.
To determine whether tocilizumab improves clinical outcomes for patients with severe or critical coronavirus disease 2019 (covid-19).
Randomised, open label trial.
Nine hospitals in Brazil, 8 May to 17 July 2020.
Adults with confirmed covid-19 who were receiving supplemental oxygen or mechanical ventilation and had abnormal levels of at least two serum biomarkers (C reactive protein, D dimer, lactate dehydrogenase, or ferritin). The data monitoring committee recommended stopping the trial early, after 129 patients had been enrolled, because of an increased number of deaths at 15 days in the tocilizumab group.
Tocilizumab (single intravenous infusion of 8 mg/kg) plus standard care (n=65) versus standard care alone (n=64).
The primary outcome, clinical status measured at 15 days using a seven level ordinal scale, was analysed as a composite of death or mechanical ventilation because the assumption of odds proportionality was not met.
A total of 129 patients were enrolled (mean age 57 (SD 14) years; 68% men) and all completed follow-up. All patients in the tocilizumab group and two in the standard care group received tocilizumab. 18 of 65 (28%) patients in the tocilizumab group and 13 of 64 (20%) in the standard care group were receiving mechanical ventilation or died at day 15 (odds ratio 1.54, 95% confidence interval 0.66 to 3.66; P=0.32). Death at 15 days occurred in 11 (17%) patients in the tocilizumab group compared with 2 (3%) in the standard care group (odds ratio 6.42, 95% confidence interval 1.59 to 43.2). Adverse events were reported in 29 of 67 (43%) patients who received tocilizumab and 21 of 62 (34%) who did not receive tocilizumab.
In patients with severe or critical covid-19, tocilizumab plus standard care was not superior to standard care alone in improving clinical outcomes at 15 days, and it might increase mortality.
ClinicalTrials.gov NCT04403685.
确定托珠单抗是否能改善重症或危重症 2019 冠状病毒病（COVID-19）患者的临床结局。
随机、开放标签试验。
2020 年 5 月 8 日至 7 月 17 日，巴西 9 家医院。
接受补充氧气或机械通气且至少两种血清生物标志物（C 反应蛋白、D 二聚体、乳酸脱氢酶或铁蛋白）水平异常的确诊 COVID-19 成人。数据监测委员会建议在入组 129 例患者后提前停止试验，因为在托珠单抗组第 15 天的死亡人数增加。
托珠单抗（单次静脉输注 8mg/kg）+标准治疗（n=65）vs 单独标准治疗（n=64）。
主要结局是采用 7 级有序量表在第 15 天测量的临床状态，分析为死亡或机械通气的复合结局，因为不符合优势比的假设。
共纳入 129 例患者（平均年龄 57（14）岁；68%为男性），所有患者均完成随访。托珠单抗组的所有患者和标准治疗组的 2 例患者均接受了托珠单抗治疗。托珠单抗组的 65 例患者中有 18 例（28%）和标准治疗组的 64 例患者中有 13 例（20%）在第 15 天需要机械通气或死亡（比值比 1.54，95%置信区间 0.66 至 3.66；P=0.32）。托珠单抗组 15 天死亡 11 例（17%），标准治疗组死亡 2 例（3%）（比值比 6.42，95%置信区间 1.59 至 43.2）。接受托珠单抗治疗的 67 例患者中有 29 例（43%）和未接受托珠单抗治疗的 62 例患者中有 21 例（34%）报告了不良事件。
在重症或危重症 COVID-19 患者中，托珠单抗联合标准治疗在第 15 天改善临床结局方面并不优于单独标准治疗，且可能增加死亡率。
ClinicalTrials.gov NCT04403685。
