Remdesivir for the Treatment of Hospitalised Patients with COVID-19 (DisCoVeRy): A Randomised, Controlled, Open-Label Trial

International audienceBackground: The antiviral efficacy of remdesivir is still controversial. We aimed at evaluating its clinical effectiveness in patients with COVID-19 requiring oxygen and/or ventilator support.Methods: In this European multicentre, open-label, parallel-group, randomised, controlled trial in adults hospitalised with COVID-19 (DisCoVeRy, NCT04315948; EudraCT2020-000936-23), participants were randomly allocated to receive usual standard of care alone or in combination with intravenous remdesivir (200 mg on day 1, then 100 mg once-daily for 9 days or until discharge). Treatment assignation was performed via web-based randomisation stratified on illness severity and administrative European region. The primary outcome was the clinical status at day 15 measured by the WHO 7-point ordinal scale, assessed in the intention-to-treat population.Findings: Between March 22nd, 2020 and January 21st, 2021, 857 participants were randomised to one of the two arms in 5 European countries and 832 participants were included for the evaluation of remdesivir (control, n=418; remdesivir, n=414). There was no difference in the clinical status neither at day 15 between treatment groups (OR for remdesivir, 0.98, 95% CI, 0.77 to 1.25, P=0.85) nor at day 29. The proportion of deaths at day 28 was not significantly different between control (8.9%) and remdesivir (8.2%) treatment groups (OR for remdesivir, 0.93 95%CI 0.57 to 1.52, P=0.77). There was also no difference on SARS-CoV-2 viral kinetics (effect of remdesivir on viral load slope, -0.004 log10 cp/10,000 cells/day, 95% CI, -0.03 to 0.02, P=0.75). There was no significant difference in the occurrence of Serious Adverse Events between treatment groups.Interpretation: The use of remdesivir for the treatment of hospitalised patients with COVID-19 was not associated with clinical improvement at day 15 or day 29, nor with a reduction in mortality, nor with a reduction in SARS-CoV-2 RNA

Remdesivir for the treatment of hospitalised patients with COVID-19: final results from the DisCoVeRy randomised, controlled, open-label trial

Background The antiviral efficacy of remdesivir is still controversial. We aimed at evaluating its clinical effectiveness in hospitalised patients with COVID-19, with indication of oxygen and/or ventilator support. Following prior publication of preliminary results, here we present the final results after completion of data monitoring. Methods In this European multicentre, open-label, parallel-group, randomised, controlled trial (DisCoVeRy, NCT04315948 ; EudraCT2020-000936-23), participants were randomly allocated to receive usual standard of care (SoC) alone or in combination with remdesivir, lopinavir/ritonavir, lopinavir/ritonavir and IFN-β-1a, or hydroxychloroquine. Adult patients hospitalised with COVID-19 were eligible if they had clinical evidence of hypoxemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzyme, severe chronic kidney disease, any contra-indication to one of the studied treatments or their use in the 29 days before randomization, or use of ribavirin, as well as pregnancy or breast-feeding. Here, we report results for remdesivir + SoC versus SoC alone. Remdesivir was administered as 200 mg infusion on day 1, followed by once daily infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. Treatment assignation was performed via web-based block randomisation stratified on illness severity and administrative European region. The primary outcome was the clinical status at day 15 measured by the WHO 7-point ordinal scale, assessed in the intention-to-treat population. Findings Between March 22 nd , 2020 and January 21 st , 2021, 857 participants were randomised to one of the two arms in 5 European countries and 843 participants were included for the evaluation of remdesivir (control, n=423; remdesivir, n=420). At day 15, the distribution of the WHO ordinal scale was as follow in the remdesivir and control groups, respectively: Not hospitalized, no limitations on activities: 62/420 (14.8%) and 72/423 (17.0%); Not hospitalized, limitation on activities: 126/420 (30%) and 135/423 (31.9%); Hospitalized, not requiring supplemental oxygen: 56/420 (13.3%) and 31/423 (7.3%); Hospitalized, requiring supplemental oxygen: 75/420 (17.9%) and 65/423 (15.4%); Hospitalized, on non-invasive ventilation or high flow oxygen devices: 16/420 (3.8%) and 16/423 (3.8%); Hospitalized, on invasive mechanical ventilation or ECMO: 64/420 (15.2%) and 80/423 (18.9%); Death: 21/420 (5%) and 24/423 (5.7%). The difference between treatment groups was not statistically significant (OR for remdesivir, 1.02, 95% CI, 0.62 to 1.70, P=0.93). There was no significant difference in the occurrence of Serious Adverse Events between treatment groups (remdesivir, n=147/410, 35.9%, versus control, n=138/423, 32.6%, p=0.29). Interpretation Remdesivir use for the treatment of hospitalised patients with COVID-19 was not associated with clinical improvement at day 15. Funding European Union Commission, French Ministry of Health, DIM One Health Île-de-France, REACTing, Fonds Erasme-COVID-ULB; Belgian Health Care Knowledge Centre (KCE), AGMT gGmbH, FEDER “European Regional Development Fund”, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. Remdesivir was provided free of charge by Gilead

Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial

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Final results of the DisCoVeRy trial of remdesivir for patients admitted to hospital with COVID-19

International audienc

Increased risk of severe COVID-19 in hospitalized patients with SARS-CoV-2 Alpha variant infection: a multicentre matched cohort study

International audienceBackground: The impact of the variant of concern (VOC) Alpha on the severity of COVID-19 has been debated. We report our analysis in France.Methods: We conducted an exposed/unexposed cohort study with retrospective data collection, comparing patients infected by VOC Alpha to contemporaneous patients infected by historical lineages. Participants were matched on age (± 2.5 years), sex and region of hospitalization. The primary endpoint was the proportion of hospitalized participants with severe COVID-19, defined as a WHO-scale > 5 or by the need of a non-rebreather mask, occurring up to day 29 after admission. We used a logistic regression model stratified on each matched pair and accounting for factors known to be associated with the severity of the disease.Results: We included 650 pairs of patients hospitalized between Jan 1, 2021, and Feb 28, 2021, in 47 hospitals. Median age was 70 years and 61.3% of participants were male. The proportion of participants with comorbidities was high in both groups (85.0% vs 90%, p = 0.004). Infection by VOC Alpha was associated with a higher odds of severe COVID-19 (41.7% vs 38.5%-aOR = 1.33 95% CI [1.03-1.72]).Conclusion: Infection by the VOC Alpha was associated with a higher odds of severe COVID-19