Antiviral drugs in hospitalized patients with COVID-19 - the DisCoVeRy trial
Authors: Ader Florence , Peiffer-Smadja Nathan , Poissy Julien , Bouscambert-Duchamp Maude , Belhadi Drifa , Diallo Alpha , Delmas Christelle , Saillard Juliette , Dechanet Aline , Mercier Noémie , Dupont Axelle , Alfaiate Toni , Lescure François-Xavier , Raffi François , Goehringer François , Kimmoun Antoine , Jaureguiberry Stéphane , Reignier Jean , Nseir Saad , Danion François , Clere-Jehl Raphael , Bouiller Kévin , Navellou Jean-Christophe , Tolsma Violaine , Cabie André , Dubost Clément , Courjon Johan , Leroy Sylvie , Mootien Joy , Gaci Rostane , Mourvillier Bruno , Faure Emmanuel , Pourcher Valérie , Gallien Sébastien , Launay Odile , Lacombe Karine , Lanoix Jean-Philippe , Makinson Alain , Martin-Blondel Guillaume , Bouadma Lila , Botelho-Nevers Elisabeth , Gagneux-Brunon Amandine , Epaulard Olivier , Piroth Lionel , Wallet Florent , Richard Jean-Christophe , Reuter Jean , Staub Thérèse , Hites Maya , Noret Marion , Andrejak Claire , Peytavin Gilles , Lina Bruno , Costagliola Dominique , Yazdanpanah Yazdan , Burdet Charles , Mentre France 
Published: January 2021

Background

Lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a and hydroxychloroquine efficacy for COVID-19 have been evaluated, but detailed evaluation is lacking.

Objective

To determine the efficacy of lopinavir/ritonavir, lopinavir/ritonavir-IFN-β-1a, hydroxychloroquine or remdesivir for improving the clinical, virological outcomes in COVID-19 inpatients.

Design

Open-label, randomized, adaptive, controlled trial.

Setting

Multi-center trial with patients from France.

Participants

583 COVID-19 inpatients requiring oxygen and/or ventilatory support

Intervention

Standard of care (SoC, control), SoC plus lopinavir/ritonavir (400 mg lopinavir and 100 mg ritonavir every 12h for 14 days), SoC plus lopinavir/ritonavir plus IFN-ß-1a (44 μg of subcutaneous IFN-ß-1a on days 1, 3, and 6), SoC plus hydroxychloroquine (400 mg twice on day 1 then 400 mg once daily for 9 days) or SoC plus remdesivir (200 mg intravenously on day 1 then 100 mg once-daily for hospitalization duration or 10 days).

Measurements

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 and safety analyses.

Results

Adjusted Odds Ratio (aOR) for the WHO 7-point ordinal scale were not in favor of investigational treatments: lopinavir/ritonavirversuscontrol, aOR 0.83, 95%CI, 0.55 to 1.26, P=0.39; lopinavir/ritonavir-IFN-β-1aversuscontrol, aOR 0.69, 95%CI, 0.45 to 1.04, P=0.08; hydroxychloroquineversuscontrol, aOR 0.93, 95%CI, 0.62 to 1.41, P=0.75. No significant effect on SARS-CoV-2 RNA clearance in respiratory tract was evidenced. Lopinavir/ritonavir-containing treatments were significantly associated with more SAE.

Limitations

Not a placebo-controlled, no anti-inflammatory agents tested.

Conclusion

No improvement of the clinical status at day 15 nor SARS-CoV-2 RNA clearance in respiratory tract specimens by studied drugs. This comforts the recent Solidarity findings.

Registration

NCT04315948.

Funding

PHRC 2020, Dim OneHealth, REACTing