卡那奴单抗对比安慰剂对住院严重 COVID-19 患者免于有创机械通气的生存影响：一项随机临床试验。
Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial.
机构信息
Division of Rheumatology, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.
Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond.
出版信息
JAMA. 2021 Jul 20;326(3):230-239. doi: 10.1001/jama.2021.9508.
IMPORTANCE
Effective treatments for patients with severe COVID-19 are needed.
OBJECTIVE
To evaluate the efficacy of canakinumab, an anti-interleukin-1β 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-<60 kg, 600 mg for 60-80 kg, and 750 mg for >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.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04362813.
重要性：需要为重症 COVID-19 患者提供有效的治疗方法。
目的：评估卡那单抗（一种抗白细胞介素-1β 的抗体）对重症 COVID-19 住院患者的疗效。
设计、地点和参与者：这是一项在欧洲和美国的 39 家医院进行的随机、双盲、安慰剂对照的 3 期临床试验。共有 454 名 COVID-19 肺炎、低氧血症（无需接受有创机械通气 [IMV]）和全身炎症反应过度的住院患者纳入研究，这些患者的血 C 反应蛋白或铁蛋白浓度升高，招募时间为 2020 年 4 月 30 日至 8 月 17 日，主要终点的最后评估时间为 2020 年 9 月 22 日。
干预措施：患者被随机分配（1:1）接受单次静脉输注卡那单抗（体重 40-<60kg 者 450mg，60-80kg 者 600mg，>80kg 者 750mg；n=227）或安慰剂（n=227）。
主要结果和测量：主要结局为第 3 天至第 29 天无需 IMV 存活。次要结局为 COVID-19 相关死亡率、全身炎症反应过度的生物标志物测量和安全性评估。
结果：在 454 名随机分组的患者中（中位年龄 59 岁，女性 187 名[41.2%]），417 名（91.9%）完成了试验的第 29 天。在第 3 天至第 29 天期间，卡那单抗组 223 名患者中有 198 名（88.8%）无需接受 IMV 存活，安慰剂组 223 名患者中有 191 名（85.7%），差异率为 3.1%（95%CI，-3.1%至 9.3%），优势比为 1.39（95%CI，0.76 至 2.54；P=0.29）。卡那单抗组 223 名患者中有 11 名（4.9%）死于 COVID-19，安慰剂组 222 名患者中有 16 名（7.2%），差异率为-2.3%（95%CI，-6.7%至 2.2%），优势比为 0.67（95%CI，0.30 至 1.50）。卡那单抗组 225 名患者中有 36 名（16%）发生严重不良事件，安慰剂组 223 名患者中有 46 名（20.6%），差异率为-4.6%（95%CI，-11.1%至 1.9%）。
结论和相关性：在因严重 COVID-19 住院的患者中，与安慰剂相比，卡那单抗治疗并未显著增加第 29 天无需 IMV 存活的可能性。
试验注册：ClinicalTrials.gov 标识符：NCT04362813。
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