Abstract:
Original Research
Losartan with add-on spironolactone for severe COVID-19 in the intensive care unit: a randomized controlled trial
Pierre Simeone a,b,* , Julien Carvelli d , Jeanne Morel a , Imane Inal a , Francois Silhol c , Bernard Vaïsse c , Camille Vaïsse c , V ´ eronique Veit e , Estelle Jean e , Baptiste Andr ´ e e , Benjamin De Sainte Marie e , Laurent Lefebvre f , Romain Ronfl ´ e f , Marc Leone g , Laurent Zieleskiewicz g , Gary Duclos g , Alexandre Lopez g , Salah Boussen a,h , Sophie Cataldi a , Xavier Roche a , Arthur Malet a , Jean-Baptiste Denis a , Alexandre Castelli a , Mehdi Assal a , Timoth ´ ee Morales a , Kevin Cot a , Thibault Pechayre a , Pierre-Henri Legal a , Marie Fleury a , Chlo ´ e Guigal a , Lucas Vizerie a , Howard Max a , David Lagier i , Benoit Guinard i , Romain Gomert i , Thibault Triglia j , Djamel Mokart k , Karine Baumstarck l , Mohamed Boucekine l , Lionel Velly a,b , Nicolas Bruder a
a Department of Anaesthesiology and Critical Care Medicine, Aix Marseille University, University Hospital Timone, Marseille, France
b CNRS, INT, Inst Neurosci Timone, Aix Marseille University, Marseille, France
c Cardiology Department, HTA and Vascular Medicine, Aix Marseille University, University Hospital Timone, Marseille, France
d Emergency Intensive Care Unit, Aix Marseille University, University Hospital Timone, Marseille, France
e Department of Internal Medicine, Aix Marseille University, University Hospital Timone, Marseille, France
f Department of Critical Care Medicine, Aix-en-Provence Hospital, Aix-en-Provence, France
- g Department of Anaesthesiology and Critical Care Medicine, Aix Marseille University, University Hospital Nord, Marseille, France
h Aix Marseille University, IFSTTAR, Marseille, 13916, France
i Department of Anesthesia and Critical Care (SAR1), Aix Marseille University, University Hospital Timone, Marseille, France
j Department of Anaesthesiology and Critical Care Medicine, Saint-Joseph Hospital, Marseille, France
k Critical Care Department, Institut Paoli Calmettes, Marseille, France
l Department of Public Health Aix Marseille University, University Hospital of Marseille, Marseille, France
A R T I C L E I N F O
Keywords: COVID-19 ARDS Renin -angiotensin system AT1R blocker
Losartan
A B S T R A C T
Background: The Coronavirus disease (COVID-19) pandemic caused significant mortality, predominantly among patients with comorbidities. Management of critically ill patients relies mainly on supportive care. SARS-CoV-2 influences the renin-angiotensin system, a potential therapeutic target. The aim was to evaluate whether losartan and spironolactone, added to standard care, improve organ failure and other clinical outcomes in patients with severe COVID-19 admitted to intensive care units. We designed a randomized, open-label, parallel-group trial, in five intensive care units in Marseille, France, from September 2020 to September 2021.
Methods: Adults with COVID-19-related respiratory distress were randomized. The experimental group received standard care plus losartan and conditional addition of spironolactone for 10 days while the control group received standard care alone. The primary endpoint was the SOFA-score on day 7. Secondary endpoints included SOFA scores at other time points, intubation rates, mechanical ventilation duration, 90-day mortality, viral replication, and safety.
Results: 78 patients were randomized (39 in the control group,..
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