Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19 A Randomized Clinical Trial
Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19 A Randomized Clinical Trial
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DOI：
10.1001/jama.2021.9508
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发表时间：
2021-07-20
影响因子：
120.7
通讯作者：
Noviello, Stephanie
中科院分区：
文献类型：
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作者：
Caricchio, Roberto;Abbate, Antonio;Noviello, Stephanie
这项临床试验比较了Canakinumab和安慰剂对重症COVID-19患者在不使用有创机械通气(IMV)的情况下生存的疗效。严重新冠肺炎患者需要重要的有效治疗。目的评价抗白细胞介素1β抗体Canakinumab治疗重症新冠肺炎的疗效。设计、设置和参与者这项随机、双盲、安慰剂对照的第三阶段试验在欧洲和美国的39家医院进行。在2020年4月30日至8月17日期间，共有454名新冠肺炎肺炎、缺氧(不需要有创机械通气)和以血C-反应蛋白或铁蛋白浓度升高为特征的全身性炎症的住院患者入选，最后一次评估主要终点是2020年9月22日。干预组患者按1：1的比例随机分为卡那普单抗(体重40~80 kg，450 mg；n=227)和安慰剂(n=227)。主要结果和指标主要结果是从第3天到第29天没有IMV的存活。次要结果是新冠肺炎相关死亡率、全身炎症生物标志物的测量和安全性评估。结果在454名随机患者中(中位年龄59岁；187名女性[41.2%])，417名(91.9%)完成了第29天的试验。在第3天到29天之间，Canakinumab组223名患者中198名(88.8%)在不需要IMV的情况下存活，而安慰剂组223名患者中有191名(85.7%)存活，比率差异为3.1%(95%可信区间，-3.1%至9.3%)，优势比为1.39(95%可信区间，0.76至2.54；P=.29)。Canakinumab组223例患者中有11例(4.9%)发生新冠肺炎相关死亡，而安慰剂组222例患者中有16例(7.2%)发生新冠肺炎相关死亡，两者的发生率差异为-2.3%(95%CI，-6.7%比2.2%)，优势比为0.67(95%CI，0.30比1.50)。接受Canakinumab治疗的225名患者中有36名(16%)观察到严重不良事件，而接受安慰剂治疗的223名患者中有46名(20.6%)观察到严重不良事件。结论和相关性在重症新冠肺炎住院患者中，与安慰剂相比，使用Canakinumab治疗并没有显著增加第29天没有IMV的生存可能性。问题：抗白细胞介素1β抗体canakinumab对治疗新冠肺炎合并炎症的患者有效吗？这项随机临床试验包括454名不需要有创机械通气的重症新冠肺炎患者，以及C反应蛋白或铁蛋白水平升高的患者。静脉注射Canakinumab与安慰剂相比，在29天内没有IMV的存活率分别为88.8%和85.7%，差异无统计学意义。这意味着在患有严重新冠肺炎的患者中，与安慰剂相比，使用Canakinumab治疗并不显著增加没有IMV的生存可能性。
This clinical trial compares the efficacy of canakinumab vs placebo on survival without invasive mechanical ventilation (IMV) in patients hospitalized with severe COVID-19.Importance Effective treatments for patients with severe COVID-19 are needed. Objective To evaluate the efficacy of canakinumab, an anti-interleukin-1 beta antibody, in patients hospitalized with severe COVID-19. Design, Setting, and Participants This randomized, double-blind, placebo-controlled phase 3 trial was conducted at 39 hospitals in Europe and the United States. A total of 454 hospitalized patients with COVID-19 pneumonia, hypoxia (not requiring invasive mechanical ventilation [IMV]), and systemic hyperinflammation defined by increased blood concentrations of C-reactive protein or ferritin were enrolled between April 30 and August 17, 2020, with the last assessment of the primary end point on September 22, 2020. Intervention Patients were randomly assigned 1:1 to receive a single intravenous infusion of canakinumab (450 mg for body weight of 40-80 kg; n = 227) or placebo (n = 227). Main Outcomes and Measures The primary outcome was survival without IMV from day 3 to day 29. Secondary outcomes were COVID-19-related mortality, measurements of biomarkers of systemic hyperinflammation, and safety evaluations. Results Among 454 patients who were randomized (median age, 59 years; 187 women [41.2%]), 417 (91.9%) completed day 29 of the trial. Between days 3 and 29, 198 of 223 patients (88.8%) survived without requiring IMV in the canakinumab group and 191 of 223 (85.7%) in the placebo group, with a rate difference of 3.1% (95% CI, -3.1% to 9.3%) and an odds ratio of 1.39 (95% CI, 0.76 to 2.54; P = .29). COVID-19-related mortality occurred in 11 of 223 patients (4.9%) in the canakinumab group vs 16 of 222 (7.2%) in the placebo group, with a rate difference of -2.3% (95% CI, -6.7% to 2.2%) and an odds ratio of 0.67 (95% CI, 0.30 to 1.50). Serious adverse events were observed in 36 of 225 patients (16%) treated with canakinumab vs 46 of 223 (20.6%) who received placebo. Conclusions and Relevance Among patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV at day 29.Question Is the anti-interleukin-1 beta antibody canakinumab effective to treat patients hospitalized with COVID-19 and hyperinflammation? Finding This randomized clinical trial included 454 patients hospitalized with severe COVID-19 not requiring invasive mechanical ventilation (IMV) and with elevated C-reactive protein or ferritin levels. Treatment with intravenous canakinumab vs placebo resulted in survival without IMV at 29 days of 88.8% vs 85.7%, a difference that was not statistically significant. Meaning Among patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV.