Abstract: medRxiv preprint doi: https://doi.org/10.1101/2020.10.06.20208066; this version posted October 8, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . TITLE: Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: Results of a target trial emulation using observational data from a nationwide Healthcare System in Peru Short Title: Target trial emulation of hydroxychloroquine, azithromycin, ivermectin. Authors: Percy Soto-Becerra1 Carlos Culquichicón1 Yamilee Hurtado-Roca1 Roger V. Araujo-Castillo1 Affiliations: 1 Instituto de Evaluación de Tecnologías en Salud e Investigación – IETSI, EsSalud, Lima, Peru. Corresponding author: Roger V. Araujo-Castillo Arenales Av. 1302, Office 310, Jesus Maria, Lima, Peru Phone number 51(1) 265-6000 - Extension 1955 araujocaroger@gmail.com Financial statement: This study was funded by the Instituto de Evaluación de Tecnologías en Salud e Investigación – IETSI, EsSalud – Peru. Conflicts of interest: The authors declare no conflicts of interest regarding the subject of this scientific article. NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.10.06.20208066; this version posted October 8, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . ABSTRACT Introduction: In Latin America, Peru is the most impacted country due to COVID-19 pandemic. Given the authorized nationwide use of hydroxychloroquine, azithromycin, ivermectin and dexamethasone in COVID-19 patients, we aimed to evaluate their effectiveness alone or combined to prevent 30-day mortality among COVID-19 hospitalized patients without life-threatening illness. Methods: Design. Retrospective cohort study using digital clinical records to emulate a target trial. Setting. Nationwide data of mid- and high-level complexity hospitals from the Peruvian Social Health Insurance (EsSalud) between April 1 and July 19, 2020. Participants. Patients aged 18 years with confirmed SARS-CoV-2 infection by PCR, and non-severe pneumonia at admission. Interventions. We compared five treatment groups to the standard of care treatment regimen (control group) within 48 hours of admission to hospital: hydroxychloroquine/chloroquine alone (HCQ), ivermectin alone (IVM), azithromycin alone (AZIT), HCQ + AZIT group, and IVM + AZIT group with doses recommended by the Peruvian Ministry of Health. Main outcomes measures. The primary outcome was all-cause mortality rate, the secondary outcomes were survival without ICU rate, and survival without oxygen prescription rate. Analyses were adjusted for confounding factors by inverse probability of treatment weighting. A doubly-adjustment method was done for sensitivity analysis. Results: Among 5683 patients eligible for analysis, 200 received hydroxychloroquine or chloroquine within 48 hours of hospital admission, 203 received ivermectin, 1600 received azithromycin, 692 received hydroxychloroquine or chloroquine plus azithromycin, 358 received..