Journal Article

Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis

Decavele, Maxens, Dres, Martin, De Sarcus, Martin, Duceau, Baptiste, Delemazure, Julie, Beurton, Alexandra, Burrel, Sonia, Clovet, Olivier, Arzoine, Jérémy, Deleris, Robin, Clarac, Ulrich, Pari, Marie Hélène, Demoule, Alexandre, Faure, Morgane, Morawiec, Elise, Virolle, Sara, Le Marec, Julien, Mayaux, Julien, Grisot, Paul Henri, Mora, Pierre, Lecronier, Marie, Boutolleau, David, Raux, Mathieu, Nemlaghi, Safaa, Bureau, Côme, Haudebourg, Luc

2020

Overview

Background The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients. Methods The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7. Results Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively ( p  = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7. Conclusion In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Antiretroviral drugs / Antiviral drugs / Care and treatment / Clinical outcomes / Clinical trials / Comparative analysis / Coronavirus Infections - drug therapy / Coronaviruses / COVID-19 / Critical care / Critical Care Medicine / Critical Illness / Drug Combinations / Emergency Medicine / Epidemics / Extracorporeal membrane oxygenation / Female / Health aspects / Humans / Hydroxychloroquine / Hydroxychloroquine - therapeutic use / Immunomodulators / Infections / Intensive / Intensive care / Intensive care unit / Life Sciences / Lopinavir - therapeutic use / Lopinavir/ritonavir / Male / Medicine / Medicine & Public Health / Middle Aged / Mortality / Pandemics / Patients / Plasma / Pneumonia / Pneumonia, Viral - drug therapy / Renal replacement therapy / Retrospective Studies / Ritonavir - therapeutic use / SARS-CoV-2 / Severe acute respiratory syndrome / Severe acute respiratory syndrome coronavirus 2 / Software / Standard of Care / Statistical analysis / Treatment Outcome / Ventilators