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Losartan with add-on spironolactone for severe COVID-19 in the intensive care unit: a randomized controlled trial

In brief

Losartan-based treatment showed no clear benefit in 78 patients with severe COVID-19

In this randomized trial, adding losartan, with spironolactone for some patients, did not significantly improve day 7 organ failure scores: median scores were 3 with standard care and 2 with treatment. Intubation, ventilation duration, 90-day mortality, and safety were also similar, but early termination left the trial too small to rule out a treatment effect.

Journal
Respiratory medicine (Q1)
Published
25 September 2026
Study design
Randomized controlled trial
Evidence level
Level 1, High (CEBM 1b)
Authors
Pierre Simeone, Julien Carvelli, Jeanne Morel, Imane Inal, Francois Silhol, Bernard Vaïsse, et al.
PMID
42790654
DOI
10.1016/j.rmed.2026.109175

Why clinicians should know about it

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.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.