Ivermectin Prophylaxis Used for COVID-19: A Citywide, Prospective, Observational Study of 223,128 Subjects Using Propensity Score Matching

Background: Ivermectin has demonstrated different mechanisms of action that potentially protect from both coronavirus disease 2019 (COVID-19) infection and COVID-19-related comorbidities. Based on the studies suggesting efficacy in prophylaxis combined with the known safety profile of ivermectin, a citywide prevention program using ivermectin for COVID-19 was implemented in Itajaí, a southern city in Brazil in the state of Santa Catarina. The objective of this study was to evaluate the impact of regular ivermectin use on subsequent COVID-19 infection and mortality rates. Materials and methods: We analyzed data from a prospective, observational study of the citywide COVID-19 prevention with ivermectin program, which was conducted between July 2020 and December 2020 in Itajaí, Brazil. Study design, institutional review board approval, and analysis of registry data occurred after completion of the program. The program consisted of inviting the entire population of Itajaí to a medical visit to enroll in the program and to compile baseline, personal, demographic, and medical information. In the absence of contraindications, ivermectin was offered as an optional treatment to be taken for two consecutive days every 15 days at a dose of 0.2 mg/kg/day. In cases where a participating citizen of Itajaí became ill with COVID-19, they were recommended not to use ivermectin or any other medication in early outpatient treatment. Clinical outcomes of infection, hospitalization, and death were automatically reported and entered into the registry in real time. Study analysis consisted of comparing ivermectin users with non-users using cohorts of infected patients propensity score-matched by age, sex, and comorbidities. COVID-19 infection and mortality rates were analyzed with and without the use of propensity score matching (PSM). Results: Of the 223,128 citizens of Itajaí considered for the study, a total of 159,561 subjects were included in the analysis: 113,845 (71.3%) regular ivermectin users and 45,716 (23.3%) non-users. Of these, 4,311 ivermectin users were infected, among which 4,197 were from the city of Itajaí (3.7% infection rate), and 3,034 non-users (from Itajaí) were infected (6.6% infection rate), with a 44% reduction in COVID-19 infection rate (risk ratio [RR], 0.56; 95% confidence interval (95% CI), 0.53-0.58; p < 0.0001). Using PSM, two cohorts of 3,034 subjects suffering from COVID-19 infection were compared. The regular use of ivermectin led to a 68% reduction in COVID-19 mortality (25 [0.8%] versus 79 [2.6%] among ivermectin non-users; RR, 0.32; 95% CI, 0.20-0.49; p < 0.0001). When adjusted for residual variables, reduction in mortality rate was 70% (RR, 0.30; 95% CI, 0.19-0.46; p < 0.0001). There was a 56% reduction in hospitalization rate (44 versus 99 hospitalizations among ivermectin users and non-users, respectively; RR, 0.44; 95% CI, 0.31-0.63; p < 0.0001). After adjustment for residual variables, reduction in hospitalization rate was 67% (RR, 0.33; 95% CI, 023-0.66; p < 0.0001). Conclusion: In this large PSM study, regular use of ivermectin as a prophylactic agent was associated with significantly reduced COVID-19 infection, hospitalization, and mortality rates.