Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial
Julio Vallejos, Rodrigo Zoni, María Bangher, Silvina Villamandos, Angelina Bobadilla, Fabian Plano, Claudia Campias, Evangelina Chaparro Campias, Maria Fernanda Medina, Fernando Achinelli, Hector Andres Guglielmone, Jorge Ojeda, Diego Farizano Salazar, Gerardo Andino, Pablo Kawerin, Silvana Dellamea, Antonia Cristina Aquino, Victor Flores, Carolina N Martemucci, Silvina Maria Martinez, Juan Emanuel Segovia, Paola Itati Reynoso, Noelia Carolina Sosa, Mariana Elizabeth Robledo, Joaquina Maria Guarrochena, Maria Mercedes Vernengo, Natalia Ruiz Diaz, Elba Meza, María Gabriela Aguirre
BMC Infectious Diseases, doi:10.1186/s12879-021-06348-5
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has changed our lives. The scientific community has been investigating re-purposed treatments to prevent disease progression in coronavirus disease patients. Objective: To determine whether ivermectin treatment can prevent hospitalization in individuals with early COVID-19. Design, setting and participants: A randomized, double-blind, placebo-controlled study was conducted in nonhospitalized individuals with COVID-19 in Corrientes, Argentina. Patients with SARS-CoV-2 positive nasal swabs were contacted within 48 h by telephone to invite them to participate. The trial randomized 501 patients between August 19th 2020 and February 22nd 2021. Intervention: Patients were randomized to ivermectin (N = 250) or placebo (N = 251) arms in a staggered dose, according to the patient's weight, for 2 days. Main outcomes and measures: The efficacy of ivermectin to prevent hospitalizations was evaluated as primary outcome. We evaluated secondary outcomes in relationship to safety and other efficacy end points.
Supplementary Information The online version contains supplementary material available at https://doi. org/10.1186/s12879-021-06348-5.
Additional file 1.
Authors' contributions
Declarations Ethics approval and consent to participate study authorized by Health Sciences Research Bioethics Committee (HSRBC) of the National University of the Northeast (UNNE) Faculty of Medicine, Argentina (Resolution 21/20 on August 17th, 2020). The consent to participate in the trial was approved by HSRBC of the UNNE. The study was performance in accordance with the Declaration of Helsinki and all methods were performed in accordance with the relevant guidelines and regulations. Informed consent was obtained from all participants prior to the study. The study has been supervised by a Steering Committee and Safety Committee.
Consent for publication Not Applicable.
Competing interests The authors declare that they have no competing interests.
Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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"abstract": "<jats:title>Abstract</jats:title><jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has changed our lives. The scientific community has been investigating re-purposed treatments to prevent disease progression in coronavirus disease (COVID-19) patients.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Objective</jats:title>\n <jats:p>To determine whether ivermectin treatment can prevent hospitalization in individuals with early COVID-19.</jats:p>\n <jats:p>Design, setting and participants: A randomized, double-blind, placebo-controlled study was conducted in non-hospitalized individuals with COVID-19 in Corrientes, Argentina. Patients with SARS-CoV-2 positive nasal swabs were contacted within 48 h by telephone to invite them to participate. The trial randomized 501 patients between August 19th 2020 and February 22nd 2021.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Intervention</jats:title>\n <jats:p>Patients were randomized to ivermectin (<jats:italic>N</jats:italic> = 250) or placebo (<jats:italic>N</jats:italic> = 251) arms in a staggered dose, according to the patient’s weight, for 2 days.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Main outcomes and measures</jats:title>\n <jats:p>The efficacy of ivermectin to prevent hospitalizations was evaluated as primary outcome. We evaluated secondary outcomes in relationship to safety and other efficacy end points.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>The mean age was 42 years (SD ± 15.5) and the median time since symptom onset to the inclusion was 4 days [interquartile range 3–6]. The primary outcome of hospitalization was met in 14/250 (5.6%) individuals in ivermectin group and 21/251 (8.4%) in placebo group (odds ratio 0.65; 95% confidence interval, 0.32–1.31; <jats:italic>p</jats:italic> = 0.227). Time to hospitalization was not statistically different between groups. The mean time from study enrollment to invasive mechanical ventilatory support (MVS) was 5.25 days (SD ± 1.71) in ivermectin group and 10 days (SD ± 2) in placebo group, (<jats:italic>p</jats:italic> = 0.019). There were no statistically significant differences in the other secondary outcomes including polymerase chain reaction test negativity and safety outcomes.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Limitations</jats:title>\n <jats:p>Low percentage of hospitalization events, dose of ivermectin and not including only high-risk population.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Conclusion</jats:title>\n <jats:p>Ivermectin had no significant effect on preventing hospitalization of patients with COVID-19. Patients who received ivermectin required invasive MVS earlier in their treatment. No significant differences were observed in any of the other secondary outcomes.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Trial registration</jats:title>\n <jats:p>ClinicalTrials.gov <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/ct2/show/NCT04529525\">NCT04529525</jats:ext-link>.</jats:p>\n </jats:sec>",
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