Remdesivir and COVID-19
Authors: Alicia Dennis
Journal: The Lancet (2020)

I commend Yeming Wang and colleagues1Wang Y Zhang D Du G et al.Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial.Lancet. 2020; 395: 1569-1578Summary Full Text Full Text PDF PubMed Scopus (2536) Google Scholar on their study in the difficult time of the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Wang and colleagues1Wang Y Zhang D Du G et al.Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial.Lancet. 2020; 395: 1569-1578Summary Full Text Full Text PDF PubMed Scopus (2536) Google Scholar calculated a sample size of 453 patients (302 to remdesivir and 151 to placebo). However, only 237 patients were enrolled and randomly assigned (158 to remdesivir and 79 to placebo). The authors' justification for not attaining the predetermined sample size was because at the time of the study, the COVID-19 outbreak was brought under control in China. This justification is not supported by the facts. Between Feb 4 and Feb 5, 2020, 1 day before study recruitment commenced, 70 people in Hubei province (China) died of COVID-19 and 3694 new cases of the disease occurred in mainland China. By Feb 6, 2020, there were 28 035 cases of COVID-19 in mainland China.2ProMed International Society for Infectious DiseasesNovel coronavirus (35): China, global, health workers, cruise, WHO, request for information.https://promedmail.org/promed-post/?id=6959291Date: 2020Date accessed: May 2, 2020Google Scholar On March 11, 2020, 1 day before the final day of the study recruitment, and the day a global pandemic was announced by WHO, there were 80 932 cases of COVID-19 in mainland China, with 4630 deaths.3ProMed International Society for Infectious DiseasesCoronavirus disease 2019 update (36): global, pandemic declared, Denmark lockdown, more countries. WHO, March 12, 2020https://promedmail.org/promed-post/?id=7079850Date accessed: May 2, 2020Google Scholar During the study period, the SARS-CoV-2 virus was not under control in China even though lockdowns had occurred.4Pueyo T Coronavirus: why you must act now.https://medium.com/@tomaspueyo/coronavirus-act-today-or-people-will-die-f4d3d9cd99caDate: March 10, 2020Date accessed: May 2, 2020Google Scholar, 5ProMed International Society for Infectious DiseasesCoronavirus disease 2019 update (19): China, Global, Italy and Iran, imported cases to new countries. WHO, Feb 26, 2020https://promedmail.org/promed-post/?id=7029842Date accessed: May 2, 2020Google Scholar Ongoing study recruitment would probably have been possible given the proportion of COVID-19 patients who become critically unwell. This recruitment would have enabled the sample size of 453 to be achieved and definitive results to be obtained. Instead, as highlighted by the authors, the study has "insufficient power to detect assumed differences in clinical outcomes".1Wang Y Zhang D Du G et al.Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial.Lancet. 2020; 395: 1569-1578Summary Full Text Full Text PDF PubMed Scopus (2536) Google Scholar It is important at this time of rapid data emergence and publication that key points regarding control, containment, infectivity, and treatments are scrutinised to the fullest degree to ensure that potentially effective treatments can be scientifically validated, and that immediate history is not incorrectly reported. I receive funding from the Australian and New Zealand College of Anaesthetists and received funding from National Health and Medical Research Council Australia from 2016–20. I am a Fellow of the Australian and New Zealand College of Anaesthetists, a member of the Australian Society of Anaesthetists, Australian Medical Association, and Australian Institute of Company Directors. I am the Australasian Representative on the Scientific Affairs Committee of the World Federation of Societies of Anaesthesiologists. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trialIn this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. Full-Text PDF Remdesivir and COVID-19The Panel on Antiretroviral Guidelines for Adults and Adolescents with HIV and the American Association for the Study of Liver Diseases guidelines for hepatitis C virus treatment suggest that combination therapy for severe acute respiratory syndrome coronavirus 2 infection will outperform single drugs. Yeming Wang and colleagues1 reported that the hazard of 28-day clinical improvement for 158 patients with severe COVID-19 randomly assigned to remdesivir was 1·2 times (95% CI 0·9 to 1·8) the hazard of patients randomly assigned to placebo, but the 28-day mortality in both these groups was similar. Full-Text PDF Remdesivir and COVID-19 – Authors' replyWe thank the clinicians and researchers around the world for their comprehensive interpretation of the results of our randomised controlled trial of remdesivir for COVID-19.1 They shared valuable thoughts from different perspectives according to related evidence from in vitro and animal models, and pharmacogenomic studies. A suggestion was made for subgroup analyses by concomitant lopinavir-ritonavir use. Concerns for not reaching the predetermined sample size in our study were also expressed. These comments are appreciated and helpful for future conduct and interpretation of COVID-19 therapy studies. Full-Text PDF Remdesivir and COVID-19In the first published placebo-controlled trial of remdesivir for treating severe COVID-19, Yeming Wang and colleagues1 were unable to attain their primary endpoint of time to clinical improvement. Although admittedly underpowered due to early trial termination, remdesivir did not appear to affect rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA load decline and mortality when compared with placebo. Given these disappointing findings, we are left to wonder if a lack of clinically significant outcomes in placebo-controlled trials could have been predicted. Full-Text PDF Remdesivir and COVID-19In a Chinese clinical trial by Yeming Wang and colleagues,1 remdesivird did not show significant benefits for patients with severe COVID-19. Shortly after their study was published, remdesivir was authorised in the USA by the US Food & Drug Administration2 and approved in Japan3 for patients with severe COVID-19 on the basis of preliminary phase 3 trial results.4 We find it puzzling that the discrepancy of results between China and the USA is merely justified by different study designs. Full-Text PDF