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

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.

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.

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.

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.