Estudo controlado de fase IIB, duplo cego e randomizado para avaliar eficácia e segurança da ivermectina em pacientes hospitalizados com Sídrome Respiratória Aguda Grave durante a pandemia de COVID-19: um ensaio clínico randomizado e revisão sistemática

Abstract

Introduction: Severe Acute Respiratory Syndrome responsible for COVID-19. COVID- 19 manifests with flu-like symptoms, potentially triggering an intensified immune response and respiratory failure. In the context of the spread of therapeutic agents for COVID 19, clinical trials have begun for some medications that could be repositioned in an attempt to minimize the serious progression of the disease, such as Ivermectin among others. Objective: To verify the efficacy and safety of using ivermectin (IVM) in association with standard treatment in the treatment of COVID 19. Material and Methods: Prospective, double-blind, randomized, placebo-controlled study with a 1:1 ratio. The inclusion criteria were patients with a positive RT-PCR test with up to seven days of symptoms, complaining of at least one flu-like symptom using supplemental oxygen therapy, aged over 18 years, and admitted to the ward. Treatment was carried out with 400 mcg/kg/day of IVM or placebo for three consecutive days, a single dose, orally. During the study, the adverse events of the included participants were monitored. The study was interrupted early due to a slow inclusion rate (competition with other studies). An updated systematic review and meta-analysis were also carried out, including randomized trials published, in 2021. Results: A total of 81 patients were included, 65% men with a mean age of 58 14 years. There was no difference between the IVM and placebo groups in relation to the need for admission to the intensive care unit (ICU) (36% vs. 33% respectively, p=0.80), the need for orotracheal intubation (28% vs. 19%, p=0.94) and death (23% vs. 10%, p=0.09). Adverse events were more frequent in the IVM group, but without statistical significance (54% vs. 40%, p= 0.42). It was observed in a metaanalysis of four studies, plus the inclusion of this one, that the use of Ivermectin has not prevented deaths (IVM, 14/160 [8.7%] vs placebo, 13/151 [8.6%]; RR, 1 .13 [95% CI, [0.57-2.25]), and in our study, the risk of death was increased in the Ivermectin group by almost 2.5 times than those in the placebo group. Conclusions: The use of Ivermectin in association with standard treatment was not superior to the use of placebo. The metaanalysis has also suggested that there is no strong scientific evidence for the use of IVM to avoid/minimize/reduce deaths; nor secondary events such as the need for mechanical ventilation and admission to the ICU.