Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial,Intensive Care Medicine

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Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial
Intensive Care Medicine ( IF 27.1 ) Pub Date : 2021-10-05 , DOI: 10.1007/s00134-021-06507-x
Ivan O Rosas ₁ , George Diaz ₂ , Robert L Gottlieb ₃ , Suzana M Lobo ₄ , Philip Robinson ₅ , Bradley D Hunter ₆ , Adilson W Cavalcante ₇ , J Scott Overcash ₈ , Nicola A Hanania ₁ , Alan Skarbnik ₉ , Julia Garcia-Diaz ₁₀ , Ivan Gordeev ₁₁ , Jordi Carratalà ₁₂ , Oliver Gordon ₁₃ , Emily Graham ₁₃ , Nicholas Lewin-Koh ₁₄ , Larry Tsai ₁₄ , Katie Tuckwell ₁₄ , Huyen Cao ₁₅ , Diana Brainard ₁₅ , Julie K Olsson ₁₄

Affiliation

Pulmonary, Critical Care, and Sleep Medicine, Lester and Sue Smith Chair in Lung Health, Baylor College of Medicine, 7200 Cambridge Street, Houston, TX, 77030, USA.
Providence Regional Medical Center Everett, Everett, WA, USA.
Baylor University Medical Center, Baylor Scott and White Research Institute, Dallas, TX, USA.
Hospital de Base de São José Do Rio Preto, São José do Rio Preto, Brazil.
Hoag Hospital, Irvine, CA, USA.
Intermountain Healthcare, Salt Lake City, UT, USA.
Centro Multidisciplinar de Estudos Clínicos, São Bernardo do Campo, Brazil.
Velocity Clinical Research, San Diego, CA, USA.
Novant Health Cancer Institute, Charlotte, NC, USA.
Ochsner Clinic Foundation, New Orleans, LA, USA.
City Clinic Hospital No. 15, Moscow, Russian Federation.
Bellvitge University Hospital, Bellvitge Biomedical Research Institute, University of Barcelona, and Spanish Network for Research in Infectious Diseases, Barcelona, Spain.
Roche Products Ltd, Welwyn Garden City, UK.
Genentech, South San Francisco, CA, USA.
Gilead Sciences, Foster City, CA, USA.

Purpose

Trials of tocilizumab in patients with severe COVID-19 pneumonia have demonstrated mixed results, and the role of tocilizumab in combination with other treatments is uncertain. Here we evaluated whether tocilizumab plus remdesivir provides greater benefit than remdesivir alone in patients with severe COVID-19 pneumonia.

Methods

This randomized, double-blind, placebo-controlled, multicenter trial included patients hospitalized with severe COVID-19 pneumonia requiring > 6 L/min supplemental oxygen. Patients were randomly assigned (2:1 ratio) to receive tocilizumab 8 mg/kg or placebo intravenously plus ≤ 10 days of remdesivir. The primary outcome was time from randomization to hospital discharge or “ready for discharge” (defined as category 1, assessed by the investigator on a 7-category ordinal scale of clinical status) to day 28. Patients were followed for 60 days.

Results

Among 649 enrolled patients, 434 were randomly assigned to tocilizumab plus remdesivir and 215 to placebo plus remdesivir. 566 patients (88.2%) received corticosteroids during the trial to day 28. Median time from randomization to hospital discharge or “ready for discharge” was 14 (95% CI 12–15) days with tocilizumab plus remdesivir and 14 (95% CI 11–16) days with placebo plus remdesivir [log-rank P = 0.74; Cox proportional hazards ratio 0.97 (95% CI 0.78–1.19)]. Serious adverse events occurred in 128 (29.8%) tocilizumab plus remdesivir and 72 (33.8%) placebo plus remdesivir patients; 78 (18.2%) and 42 (19.7%) patients, respectively, died by day 28.

Conclusions

Tocilizumab plus remdesivir did not shorten time to hospital discharge or “ready for discharge” to day 28 compared with placebo plus remdesivir in patients with severe COVID-19 pneumonia.

中文翻译：

托珠单抗和瑞德西韦治疗重症 COVID-19 肺炎住院患者：一项随机临床试验

目的

托珠单抗在重症 COVID-19 肺炎患者中的试验结果喜忧参半，托珠单抗与其他治疗联合的作用尚不确定。在这里，我们评估了托珠单抗加瑞德西韦在重症 COVID-19 肺炎患者中是否比单独使用瑞德西韦提供更大的益处。

方法

这项随机、双盲、安慰剂对照、多中心试验纳入了因严重 COVID-19 肺炎住院的患者，需要 > 6 L/min 的补充氧气。患者被随机分配（2:1 比例）接受托珠单抗 8 mg/kg 或静脉内安慰剂加 ≤ 10 天的瑞德西韦。主要结果是从随机分组到出院或“准备出院”（定义为第 1 类，由研究者根据临床状态的 7 类序数量表评估）到第 28 天的时间。对患者进行了 60 天的随访。

结果

在 649 名入组患者中，434 名被随机分配到托珠单抗加瑞德西韦组，215 名被随机分配到安慰剂加瑞德西韦组。566 名患者 (88.2%) 在试验期间至第 28 天接受了皮质类固醇治疗。从随机分组到出院或“准备出院”的中位时间为 14 (95% CI 12-15) 天，托珠单抗加瑞德西韦和 14 (95% CI 11 –16) 安慰剂加瑞德西韦天数 [log-rank P = 0.74; Cox 比例风险比 0.97 (95% CI 0.78–1.19)]。128 名（29.8%）托珠单抗加瑞德西韦患者和 72 名（33.8%）安慰剂加瑞德西韦患者发生严重不良事件；分别有 78 名 (18.2%) 和 42 名 (19.7%) 患者在第 28 天死亡。