RESUMO
BackgroundACEi/ARB medications have been hypothesized to have potential benefit in COVID-19. Despite concern for increased ACE-2 expression in some animal models, preclinical and observational-retrospective and uncontrolled trials suggested possible benefit. Two RCTs of the ARB losartan from University of Minnesota showed no benefit yet safety signals for losartan in outpatient and hospitalized COVID-19 patients. COVID MED, started early in the pandemic, also assessed losartan in a RCT in hospitalized patients with COVID-19. MethodsCOVID MED was a double-blinded, placebo-controlled, multicenter, platform randomized clinical trial (RCT). Hospitalized COVID-19 patients were randomized to receive standard care and hydroxychloroquine, lopinavir/ritonavir, losartan, or placebo. Hydroxychloroquine and lopinavir/ritonavir arms were discontinued after RCTs showed no benefit. We report data from the losartan arm compared to combined (lopinavir-ritonavir and placebo) and prespecified placebo-only controls. The primary endpoint, the mean COVID-19 Ordinal Severity Score (COSS) slope of change, was compared with the Students t-test. Slow enrollment prompted early termination. ResultsOf 448 screened patients, 15 (3.5%) were randomized/enrolled, 9 to receive losartan and 6 to receive control (lopinavir/ritonavir [N=2], placebo [N=4]); 1 patient who withdrew prior to study drug was excluded yielding 14 patients for analysis (losartan [N=9] vs. control [N=5] [lopinavir/ritonavir [N=2], placebo [N=3]]). Most baseline parameters were balanced. Treatment with losartan was not associated with a difference in mean COSS slope of change in comparison with combined control (p=0.4) or placebo-only control (p=0.05) (trend favoring placebo). 60-day mortality and overall AE and SAE rates were numerically but not significantly higher with losartan. ConclusionsIn this small blinded RCT in hospitalized COVID-19 patients, losartan did not improve outcome vs. control comparisons and was associated with adverse safety signals.
