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.
RESUMO
IntroductionTocilizumab is an anti-interleukin-6 antibody that has been used for the treatment of severe coronavirus disease 2019 (COVID-19). However, the concrete evidence of its benefit in reducing the mortality in severe COVID-19 is lacking. Therefore, we performed a systematic review and meta-analysis of relevant studies that compared the efficacy of Tocilizumab in severe COVID-19 vs. standard of care alone. MethodsLiterature search for studies that compared Tocilizumab and Standard of care in the treatment of COVID-19 was done using major online databases from December 2019 to June 14th, 2020. Search words Tocilizumab, anti-interleukin-6 antibody, and COVID-19 or coronavirus 2019 in various combinations were used. Articles in the form of abstracts, letters without original data, case reports, and reviews were excluded. Data was gathered on an excel sheet, and statistical analysis was performed using Review Manager 5.3. ResultsSixteen studies were eligible from 693 initial studies, including 3,641 patients (64% males). There were thirteen retrospective studies and three prospective studies. There were 2,488 patients in the standard of care group (61.7%) and 1,153 patients (68.7%) in the Tocilizumab group. The death rate in the tocilizumab group, 22.4% (258/1153), was lower than the standard of care group, 26.21% (652/2,488) (Pooled odds ratio 0.57 [95% CI 0.36-0.92] p=0.02). There was a significant heterogeneity (Inconsistency index= 80%) among the included studies. ConclusionThe addition of Tocilizumab to the standard of care might reduce the mortality in severe COVID-19. Larger randomized clinical trials are needed to validate these findings.
