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Tocilizumab Ameliorates the Hypoxia in COVID-19 Moderate Patients with Bilateral Pulmonary Lesions: A Randomized, Controlled, Open-Label, Multicenter Trial

19 Pages Posted: 29 Aug 2020

See all articles by Dongsheng Wang

Dongsheng Wang

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of University of Science and Technology of China

Binqing Fu

University of Science and Technology of China (USTC) - Division of Molecular Medicine

Zhen Peng

Drug Clinical Trail Institution, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China

Dongliang Yang

Huazhong University of Science and Technology (Formerly Tongi Medical University) - Department of Infectious Diseases

Mingfeng Han

Fuyang 2nd People’s Hospital - Department of Internal Medicine

Min Li

Hunan Provincial Clinical Research Center for Respiratory Disease

Yun Yang

ntensive Care Unit, The First Affiliated Hospital of University of Science and Technology of China

Tianjun Yang

Intensive Care Unit, the First Affiliated Hospital of University of Science and Technology of China

Liangye Sun

u'an people's Hospital affiliated to Anhui Medical University

Wei Li

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Bengbu Medical College, Clinical Research Center for Respiratory Disease

Wei Shi

Anhui Medical University - Department of Respiratory Medicine

Xin Yao

First Affiliated Hospital of Nanjing Medical University

Yan Ma

Department of Rheumatology and Immunology, the First Affiliated Hospital of University of Science and Technology of China

Xiao jing Wang

Department of Endocrinology, the First Affiliated Hospital of University of Science and Technology of China

Jun Chen

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of University of Science and Technology of China

Daqing Xia

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of University of Science and Technology of China

Yubei Sun

Department of Oncology, the First Affiliated Hospital of University of Science and Technology of China

Lin Dong

Department of Endocrinology, the First Affiliated Hospital of University of Science and Technology of China

Jumei Wang

Department of Endocrinology, the First Affiliated Hospital of University of Science and Technology of China

Xiaoyu Zhu

Department of Hematology, the First Affiliated Hospital of University of Science and Technology of China

Yonggang Zhou

Division of Life Sciences and Medicine, University of Science and Technology of China

Aijun Pan

Intensive Care Unit, the First Affiliated Hospital of University of Science and Technology of China

Xiaowen Hu

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of University of Science and Technology of China

Xiaodong Mei

University of Science and Technology of China (USTC) - Division of Molecular Medicine; University of Science and Technology of China (USTC) - Institute of Immunology

Haiming Wei

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of University of Science and Technology of China

Xiaoling Xu

University of Science and Technology of China (USTC) - Department of Pulmonary and Critical Care Medicine

More...

Abstract

Background: Tocilizumab is reported to be able to attenuate the "cytokine storm" in COVID-19 patients. We tried to ascertain the effectiveness and safety of tocilizumab in COVID-19 and identify patients most likely to be benefit from the treatment.

Methods: This was a randomized, controlled, open-label, multicenter trial at 6 hospitals in Anhui and Hubei. Patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care, or standard care alone. The first dose of tocilizumab was 400 mg, diluted in 100 ml 0.9% saline, and intravenous dripped in more than 1 h. A second dose was given if a patient remained febrile for 24 hours after the first dose. The primary endpoint was the cure rate. Primary analysis was done in the intention -to -treat (ITT) population and safety analysis was done in all patients who started their assigned treatment.

Findings: Between Feb 13, 2020, and March 13, 2020, 65 patients were enrolled and randomly assigned to a treatment group (33 to tocilizumab and 32 to the controls). One patient in the control group, who aggravated severely 3 days after randomization, was transferred to the tocilizumab group. The cure rate in tocilizumab group was higher than that in the controls but not significant (94.12% vs 87.10%, P=0.4133). Adverse events were recorded in 20 (58.82%) of 34 tocilizumab recipients versus 4 (12.90%) of 31 in the controls. No serious adverse events were reported in tocilizumab group.  

Interpretation: Tocilizumab treatment did not increase the cure rate of COVID-19. A large scale of study enrolling more patients is needed. However,tocilizumab can improve oxygenation without significant influence on the time virus load tunes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab should be recommended for better disease management.

Trial Registration: This trial was registered in Chinese Clinical Trial Registry (Number: ChiCTR2000029765).

Funding: This work was supported by Department of Science and Technology of Anhui Province and Health Commission of Anhui Province (grant number: 202004a07020001) and the China National Center for Biotechnology Development (grant number: 2020YFC0843800).

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: The study protocol was approved by the Medical Research Ethics Committee of Anhui Provincial Hospital, the First Affiliated Hospital of USTC [approval no. 2020-XG (H)-015]. The authors committed to protect the patient’s privacy and comply with the Helsinki Declaration.

Keywords: Tocilizumab, Covid-19, cytokine storm

Suggested Citation

Wang, Dongsheng and Fu, Binqing and Peng, Zhen and Yang, Dongliang and Han, Mingfeng and Li, Min and Yang, Yun and Yang, Tianjun and Sun, Liangye and Li, Wei and Shi, Wei and Yao, Xin and Ma, Yan and Wang, Xiao jing and Chen, Jun and Xia, Daqing and Sun, Yubei and Dong, Lin and Wang, Jumei and Zhu, Xiaoyu and Zhou, Yonggang and Pan, Aijun and Hu, Xiaowen and Mei, Xiaodong and Wei, Haiming and Xu, Xiaoling, Tocilizumab Ameliorates the Hypoxia in COVID-19 Moderate Patients with Bilateral Pulmonary Lesions: A Randomized, Controlled, Open-Label, Multicenter Trial. Available at SSRN: https://ssrn.com/abstract=3667681 or http://dx.doi.org/10.2139/ssrn.3667681

Dongsheng Wang

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of University of Science and Technology of China

Binqing Fu

University of Science and Technology of China (USTC) - Division of Molecular Medicine

Hefei
China

Zhen Peng

Drug Clinical Trail Institution, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China

Dongliang Yang

Huazhong University of Science and Technology (Formerly Tongi Medical University) - Department of Infectious Diseases ( email )

Wuhan
China

Mingfeng Han

Fuyang 2nd People’s Hospital - Department of Internal Medicine

Fuyang, 236015
China

Min Li

Hunan Provincial Clinical Research Center for Respiratory Disease

Yun Yang

ntensive Care Unit, The First Affiliated Hospital of University of Science and Technology of China

Tianjun Yang

Intensive Care Unit, the First Affiliated Hospital of University of Science and Technology of China ( email )

Liangye Sun

u'an people's Hospital affiliated to Anhui Medical University ( email )

Wei Li

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Bengbu Medical College, Clinical Research Center for Respiratory Disease

Wei Shi

Anhui Medical University - Department of Respiratory Medicine ( email )

Anqing, Anhui 246000
China

Xin Yao

First Affiliated Hospital of Nanjing Medical University

Yan Ma

Department of Rheumatology and Immunology, the First Affiliated Hospital of University of Science and Technology of China

Xiao jing Wang

Department of Endocrinology, the First Affiliated Hospital of University of Science and Technology of China ( email )

Jun Chen

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of University of Science and Technology of China

Daqing Xia

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of University of Science and Technology of China ( email )

Yubei Sun

Department of Oncology, the First Affiliated Hospital of University of Science and Technology of China ( email )

Lin Dong

Department of Endocrinology, the First Affiliated Hospital of University of Science and Technology of China ( email )

Jumei Wang

Department of Endocrinology, the First Affiliated Hospital of University of Science and Technology of China ( email )

Xiaoyu Zhu

Department of Hematology, the First Affiliated Hospital of University of Science and Technology of China

Yonggang Zhou

Division of Life Sciences and Medicine, University of Science and Technology of China ( email )

Aijun Pan

Intensive Care Unit, the First Affiliated Hospital of University of Science and Technology of China ( email )

Xiaowen Hu

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of University of Science and Technology of China

Xiaodong Mei (Contact Author)

University of Science and Technology of China (USTC) - Division of Molecular Medicine ( email )

Hefei
China

University of Science and Technology of China (USTC) - Institute of Immunology ( email )

Hefei
China

Haiming Wei

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of University of Science and Technology of China

Xiaoling Xu

University of Science and Technology of China (USTC) - Department of Pulmonary and Critical Care Medicine ( email )

Hefei
China

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