Title :

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

Author(s) :

Ader, Florence [Auteur]
Peiffer-Smadja, Nathan [Auteur]
Poissy, Julien [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Bouscambert-Duchamp, Maude [Auteur]
Belhadi, Drifa [Auteur]
Diallo, Alpha [Auteur]
Delmas, Christelle [Auteur]
Saillard, Juliette [Auteur]
Dechanet, Aline [Auteur]
Mercier, Noémie [Auteur]
Dupont, Axelle [Auteur]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Alfaiate, Toni [Auteur]
Lescure, François-Xavier [Auteur]
Raffi, François [Auteur]
Goehringer, François [Auteur]
Kimmoun, Antoine [Auteur]
Jaureguiberry, Stéphane [Auteur]
Reignier, Jean [Auteur]
Nseir, Saad [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Danion, François [Auteur]
Clere-Jehl, Raphael [Auteur]
Bouiller, Kévin [Auteur]
Navellou, Jean-Christophe [Auteur]
Tolsma, Violaine [Auteur]
Cabié, André [Auteur]
Dubost, Clément [Auteur]
Courjon, Johan [Auteur]
Leroy, Sylvie [Auteur]
Mootien, Joy [Auteur]
Gaci, Rostane [Auteur]
Mourvillier, Bruno [Auteur]
Faure, Emmanuel [Auteur]
Université Lille Nord de France (COMUE)
Pourcher, Valérie [Auteur]
Gallien, Sébastien [Auteur]
Launay, Odile [Auteur]
Lacombe, Karine [Auteur]
Lanoix, Jean-Philippe [Auteur]
Makinson, Alain [Auteur]
Martin-Blondel, Guillaume [Auteur]
Bouadma, Lila [Auteur]
Botelho-Nevers, Elisabeth [Auteur]
Gagneux-Brunon, Amandine [Auteur]
Epaulard, Olivier [Auteur]
Piroth, Lionel [Auteur]
Wallet, Florent [Auteur]
Richard, Jean-Christophe [Auteur]
Reuter, Jean [Auteur]
Staub, Thérèse [Auteur]
Lina, Bruno [Auteur]
Noret, Marion [Auteur]
Andrejak, Claire [Auteur]
Lê, Minh Patrick [Auteur]
Peytavin, Gilles [Auteur]
Hites, Maya [Auteur]
Costagliola, Dominique [Auteur]
Yazdanpanah, Yazdan [Auteur]
Burdet, Charles [Auteur]
Mentré, France [Auteur]

Journal title :

Clinical Microbiology and Infection

Abbreviated title :

Clinical Microbiology and Infection

Volume number :

27

Pages :

1826-1837

Publisher :

Elsevier BV

Publication date :

2021-12

ISSN :

1198-743X

English keyword(s) :

COVID-19
Hydroxychloroquine
Interferon β-1a
Lopinavir/ritonavir
Randomized controlled trial
SARS-CoV-2

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Objectives We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir–interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in ...
Show more >Objectives We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir–interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support. Methods We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely. Results The intention-to-treat population included 583 participants—lopinavir/ritonavir (n = 145), lopinavir/ritonavir–IFN–β-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)—among whom 418 (71.7%) were male, the median age was 63 years (IQR 54–71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55–1.26, p 0.39), lopinavir/ritonavir–IFN–β-1a versus control, aOR 0.69 (95%CI 0.45–1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62–1.41, p 0.75). 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. Conclusion In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir–IFN–β-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Glycobiology in fungal Pathogenesis and Clinical Applications

Submission date :

2024-03-04T10:05:24Z
2024-03-05T10:52:01Z
2024-03-05T13:23:41Z