Remdesivir for the treatment of hospitalised patients with COVID-19: final results from the DisCoVeRy randomised, controlled, open-label trial
Authors: Ader Florence , Bouscambert-Duchamp Maude , Hites Maya , Peiffer-Smadja Nathan , Poissy Julien , Belhadi Drifa , Diallo Alpha , Delmas Christelle , Saillard Juliette , Dechanet Aline , Fougerou Claire , Lê Minh-Patrick , Peytavin Gilles , Mercier Noémie , Velou Priyanka , Tubiana Sarah , Lescure Xavier , Faure Emmanuel , Nseir Saad , Richard Jean-Christophe , Wallet Florent , Goehringer François , Lefèvre Benjamin , Kimmoun Antoine , Raffi François , Gaborit Benjamin , Reignier Jean , Lanoix Jean-Philippe , Andrejak Claire , Zerbib Yoann , Bani-Sadr Firouzé , Mourvilliers Bruno , Danion François , Ruch Yvon , Clere-Jehl Raphaël , Le Moing Vincent , Klouche Kada , Lacombe Karine , Martin-Blondel Guillaume , Vardon-Bounes Fanny , Cabié André , Turmel Jean-Marie , Piroth Lionel , Blot Mathieu , Botelho-Nevers Élisabeth , Gagneux-Brunon Amandine , Thiery Guillaume , Bénézit François , Gaci Rostane , Mootien Joy , Gallien Sébastien , Garot Denis , Bouiller Kevin , Epelboin Loïc , Jauréguiberry Stéphane , Gaymard Alexandre , Verschelden Gil , Braz Sandra , Ferreira Ribeiro Joao Miguel , Joannidis Michael , Staub Thérèse , Altdorfer Antoine , Greil Richard , Egle Alexander , Guedj Jérémie , Noret Marion , Roncon-Albuquerque Roberto , Paiva Jose-Artur , Lina Bruno , Costagliola Dominique , Yazdanpanah Yazdan , Burdet Charles , Mentré France 
Published: April 2022

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 22nd, 2020 and January 21st, 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.