Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial
Yeming Wang, Dingyu Zhang, Prof Guanhua Du, Ronghui Du, MD Jianping Zhao, Yang Jin, Prof Shouzhi Fu, Prof Ling Gao, Prof Zhenshun Cheng, Prof Qiaofa Lu, Yi Hu, Guangwei Luo, Ke Wang, Yang Lu, Huadong Li, Shuzhen Wang, Shunan Ruan, Chengqing Yang, Chunlin Mei, MD, D Ding MD Yi Wang, Dan Ding, Feng Wu, Xin Tang, Xianzhi Ye, Yingchun Ye, Bing Liu, Jie Yang, Wen Yin, Aili Wang, Guohui Fan, Fei Zhou, Zhibo Liu, Xiaoying Gu, Jiuyang Xu, Lianhan Shang, Yi Zhang, Lianjun Cao, Tingting Guo, Yan Wan, Hong Qin, Yushen Jiang, Thomas Jaki, Frederick G Hayden, Peter W Horby, Prof Bin Cao, Prof Chen Wang
The Lancet, doi:10.1016/s0140-6736(20)31022-9
Background No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. Methods We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656.
with a previous study of compassionate use of remdesivir, 21 our study population was less ill (eg, at the time of enrolment, 0•4% were on invasive mechanical ventilation or extracorporeal membrane oxygenation vs 64% in the previous study) and was treated somewhat earlier in their disease course (median 10 days vs 12 days). Such differences might be expected to favour remdesivir, providing greater effects in our study population, but our results did not meet this expectation. However, our study did not reach its target enrolment because the stringent public health measures used in Wuhan led to marked reductions in new patient presentations in mid-March, and restrictions on hospital bed availability resulted in most patients being enrolled later in the course of disease. Consequently, we could not adequately assess whether earlier remdesivir treatment might have provided clinical benefit. However, among patients who
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