tetano
Editor, Senior Moderator
Respir Med
. 2026 Sep 25:263:109175.
doi: 10.1016/j.rmed.2026.109175. Online ahead of print.
Pierre Simeone 1 , Julien Carvelli 2 , Jeanne Morel 3 , Imane Inal 3 , Francois Silhol 4 , Bernard Vaïsse 4 , Camille Vaïsse 4 , Véronique Veit 5 , Estelle Jean 5 , Baptiste André 5 , Benjamin De Sainte Marie 5 , Laurent Lefebvre 6 , Romain Ronflé 6 , Marc Leone 7 , Laurent Zieleskiewicz 7 , Gary Duclos 7 , Alexandre Lopez 7 , Salah Boussen 8 , Sophie Cataldi 3 , Xavier Roche 3 , Arthur Malet 3 , Jean-Baptiste Denis 3 , Alexandre Castelli 3 , Mehdi Assal 3 , Timothée Morales 3 , Kevin Cot 3 , Thibault Pechayre 3 , Pierre-Henri Legal 3 , Marie Fleury 3 , Chloé Guigal 3 , Lucas Vizerie 3 , Howard Max 3 , David Lagier 9 , Benoit Guinard 9 , Romain Gomert 9 , Thibault Triglia 10 , Djamel Mokart 11 , Karine Baumstarck 12 , Mohamed Boucekine 12 , Lionel Velly 13 , Nicolas Bruder 3
Affiliations Expand
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, 39 in the experimental group); the primary outcome was analysed in 73 patients (the modified intention-to-treat population comprised 74; one experimental patient died on day 6). We found no significant difference in median SOFA-score on day 7 between the groups (3 vs 2; p = 0.5). There were no significant differences in intubation rates, mechanical ventilation duration, 90-day mortality, or adverse events. Viral replication and oxygenation parameters were also similar.
Conclusion: This trial did not detect a statistically significant treatment effect of losartan, with spironolactone added in a minority of patients, on clinical outcomes in COVID-19 ICU patients. However, the trial was underpowered due to early termination.
Keywords: ARDS; AT1R blocker; COVID-19; Losartan; Renin–angiotensin system.
. 2026 Sep 25:263:109175.
doi: 10.1016/j.rmed.2026.109175. Online ahead of print.
Losartan with add-on spironolactone for severe COVID-19 in the intensive care unit: a randomized controlled trial
Pierre Simeone 1 , Julien Carvelli 2 , Jeanne Morel 3 , Imane Inal 3 , Francois Silhol 4 , Bernard Vaïsse 4 , Camille Vaïsse 4 , Véronique Veit 5 , Estelle Jean 5 , Baptiste André 5 , Benjamin De Sainte Marie 5 , Laurent Lefebvre 6 , Romain Ronflé 6 , Marc Leone 7 , Laurent Zieleskiewicz 7 , Gary Duclos 7 , Alexandre Lopez 7 , Salah Boussen 8 , Sophie Cataldi 3 , Xavier Roche 3 , Arthur Malet 3 , Jean-Baptiste Denis 3 , Alexandre Castelli 3 , Mehdi Assal 3 , Timothée Morales 3 , Kevin Cot 3 , Thibault Pechayre 3 , Pierre-Henri Legal 3 , Marie Fleury 3 , Chloé Guigal 3 , Lucas Vizerie 3 , Howard Max 3 , David Lagier 9 , Benoit Guinard 9 , Romain Gomert 9 , Thibault Triglia 10 , Djamel Mokart 11 , Karine Baumstarck 12 , Mohamed Boucekine 12 , Lionel Velly 13 , Nicolas Bruder 3
Affiliations Expand
- PMID: 42790654
- DOI: 10.1016/j.rmed.2026.109175
Abstract
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, 39 in the experimental group); the primary outcome was analysed in 73 patients (the modified intention-to-treat population comprised 74; one experimental patient died on day 6). We found no significant difference in median SOFA-score on day 7 between the groups (3 vs 2; p = 0.5). There were no significant differences in intubation rates, mechanical ventilation duration, 90-day mortality, or adverse events. Viral replication and oxygenation parameters were also similar.
Conclusion: This trial did not detect a statistically significant treatment effect of losartan, with spironolactone added in a minority of patients, on clinical outcomes in COVID-19 ICU patients. However, the trial was underpowered due to early termination.
Keywords: ARDS; AT1R blocker; COVID-19; Losartan; Renin–angiotensin system.