An open-label randomized, controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19 – Final results from the DisCoVeRy trial
M.D Florence Ader, Nathan Peiffer-Smadja, Julien Poissy, Maude Bouscambert-Duchamp, Drifa Belhadi, Alpha Diallo, Christelle Delmas, Juliette Saillard, Aline Dechanet, Noémie Mercier, Axelle Dupont, Toni Alfaiate, François-Xavier Lescure, François Raffi, François Goehringer, Antoine Kimmoun, Stéphane Jaureguiberry, Jean Reignier, Saad Nseir, François Danion, Raphael Clere-Jehl, Kévin Bouiller, Jean-Christophe Navellou, Violaine Tolsma, André Cabie, Clément Dubost, Johan Courjon, Sylvie Leroy, Joy Mootien, Rostane Gaci, Bruno Mourvillier, Emmanuel Faure, Valérie Pourcher, Sébastien Gallien, Odile Launay, Karine Lacombe, Jean-Philippe Lanoix, Alain Makinson, Guillaume Martin-Blondel, Lila Bouadma, Elisabeth Botelho-Nevers, Amandine Gagneux-Brunon, Olivier Epaulard, Lionel Piroth, Florent Wallet, Jean-Christophe Richard, Jean Reuter, Thérèse Staub, Bruno Lina, Marion Noret, Claire Andrejak, Minh Patrick Lê, Gilles Peytavin, Maya Hites, Dominique Costagliola, Yazdan Yazdanpanah, Charles Burdet, France Mentre
doi:10.1101/2022.02.16.22271064
An open-label randomized, controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19 -Final results from the DisCoVeRy trial.
Authors contribution Writing -Original Draft: FA, CB; Writing -Review & Editing: NPS, JP, MBD, DB, ADi, MH, MPL, GP, DC, YY, FM; Conceptualization: FA, NPS, JP, MBD, GP, BL, DC, YY, FM; Investigation: FA, NPS, JP, MBD, Adi, NM, FXL, FR, FG, AK, SJ, JR, SN, FD, RCJ, KB, JCN, VT, AC, CDu, JC, SL, JM, RG, BM, EF, VP, SG, OL, KL, JPL, AM, GMB, LB, ÉBN, AGB, OE, LP, FW, JCR, JR, TS, MH, CA, MPL, GP; Methodology: FA, NPS, JP, MBD, DC, CB, FM; Data curation: ADi, ADe, NM, ADu, TA; Formal Analysis: DB, ADu, DC, CB, FM Project Administration: FA, CD, FM; Funding Acquisition: FA, CDe, JS, DC, YY, FM.
Declaration of interests F.R. reports personal fees from Gilead Sciences, personal fees from MSD, personal fees from Pfizer, personal fees from TheraTechnologies, personal fees from ViiV Healthcare, outside the submitted work. F.G. reports grants from BioMerieux, personal fees and non-financial support from Gilead, non-financial support from Corevio, outside the submitted work. G.P. reports grants and personal fees from Gilead Sciences, grants and personal fees from Merck, grants and personal fees from ViiV Healthcare, grants and personal fees from TheraTechnologies, outside the submitted work. K.L. reports personal fees and non-financial support from Gilead, personal fees and non-financial support from Janssen, personal fees and non-financial support from MSD, personal fees and non-financial support from ViiV Healthcare, personal fees and non-financial support from Abbvie, during..
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DOI record:
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"DOI": "10.1101/2022.02.16.22271064",
"URL": "http://dx.doi.org/10.1101/2022.02.16.22271064",
"abstract": "<jats:p>Objectives\nWe evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-beta-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in COVID-19 inpatients requiring oxygen and/or ventilatory support. While preliminary results were previously published, we present here the final results, following completion of the data monitoring.\nMethods\nWe conducted a phase 3 multi-centre open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), add-on trial to Solidarity (<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04315948\">NCT04315948</jats:ext-link>, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO 7-point ordinal scale. Secondary outcomes included SARS-CoV-2 quantification in respiratory specimens, pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, which were stopped prematurely.\nResults\nThe intention-to-treat population included 593 participants (lopinavir/ritonavir, n=147; lopinavir/ritonavir-IFN-beta-1a, n=147; hydroxychloroquine, n=150; control, n=149), among whom 421 (71.0%) were male, the median age was 64 years (IQR, 54-71) and 214 (36.1%) had a severe disease. The day 15 clinical status was not improved with investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.82, (95% confidence interval [CI] 0.54-1.25, P=0.36); lopinavir/ritonavir-IFN-beta-1a versus control, aOR 0.69 (95%CI 0.45-1.05, P=0.08); hydroxychloroquine versus control, aOR 0.94 (95%CI 0.62-1.41, P=0.76). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of Serious Adverse Events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms. \nConclusion\nIn adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-beta-1a and hydroxychloroquine did not improve the clinical status at day 15, nor SARS-CoV-2 clearance in respiratory tract specimens.</jats:p>",
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