key: cord-0258629-3zkf85e4 authors: Roy-Garcia, I. A.; Moreno-Noguez, M.; Rivas-Ruiz, R.; Zapata-Tarres, M.; Perez-Rodriguez, M.; Ortiz-Zamora, M. A.; Navarro-Susano, G.; Guzman-Rivas, L.; Garcia-Cortes, L. R.; Palma-Lara, I.; Gutierrez-Catrellon, P. title: Efficacy and Safety of Fixed Combination of Hydroxychloroquine with Azithromycin Versus Hydroxychloroquine and Placebo in Patients with Mild COVID-19: Randomized, double blind, Placebo controlled trial date: 2022-04-16 journal: nan DOI: 10.1101/2022.04.06.22273531 sha: 4b6b05580e9073a1ab0bcc1c19dbb32e6643d5dd doc_id: 258629 cord_uid: 3zkf85e4 To determine the efficacy and safety of fixed combination of hydroxychloroquine/azithromycin (HCQ+AZT) compared to hydroxychloroquine (HCQ) alone or placebo in mild COVID-19 outpatients to avoid hospitalization.Materials and methods This randomized, parallel, double-blind clinical trial included male and female patients aged 18 and 76 years non COVID vaccinated, who were diagnosed with mild COVID-19 infection. All patients underwent liver and kidney profile test, as well as a health questionnaire and clinical revision to document that they did not have uncontrolled comorbidities. They were randomly assigned to one of the three treatment arms: 1) hydroxychloroquine with azithromycin 200 mg/250 mg every 12 hours for five days followed by hydroxychloroquine 200 mg every 12 hours for 5 days; 2) hydroxychloroquine 200 mg every 12 hours for ten days; or 3) placebo every 12 hours for ten days. The primary outcome of the study was hospitalization, while the secondary outcomes were disease progression, pneumonia, use of supplemental oxygen, and adverse events. This study was registered in clinicaltrials.gov with the NCT number of 04964583.ResultsA total of 92 participants were randomized. Of whom, 30 received HCQ+AZT, 31 received HCQ, and 31 received placebo. The median age was 37 years, 27.2% of the participants had comorbidities, and the global incidence of hospitalization was 2.2%. The incidence of hospitalization was 6.7% (2/30) in the HCQ+AZT group compared to the HCQ or placebo groups, in which there were no hospitalizations. Progression of disease was higher in the HCQ group [RR=3.25 (95% CI, 1.19-8.87)] compared with placebo group. There was no statistical difference between the HCQ+AZT group and the placebo group in progression of disease. The incidence of pneumonia was 30% in the HCQ+AZT group, 32.2% in the HCQ group, and 9.6% in the placebo group (HCQ + AZT vs Placebo; p=0.06). There was a significant risk of pneumonia versus placebo only in the HCQ group [RR=3.33 (95% CI, 1.01-10.9)]. Supplemental oxygen was required by 20% (6/30) of the patients in the HCQ+AZT group, 6.4 (2/31) of the patients in the HCQ group, and 3.2% (1/31) of the patients in the placebo group,[(HCQ + AZT vs Placebo; p=0.100), (HCQ vs Placebo, p=0.610)]. There was no statistical difference between groups for negative test (PCR) on day 11. The most frequent adverse events were gastrointestinal symptoms. No lengthening of the QT interval was observed in patients receiving HCQ+AZT or HCQ.ConclusionThe use of HCQ+AZT does not decrease the risk of hospitalization in patients with mild COVID-19. The use of HCQ increases the risk of progression and pneumonia. 7 122 or conjunctivitis [14] . The diagnosis was confirmed by RT-PCR for SARS-CoV-2, the 123 severity of the disease was evaluated with the NEWS scale, patients with a score ≤4 124 points were considered to have mild disease. Patients with cardiac disorders with 125 delayed cardiac conduction (QT segment ≥ 450 ms), pregnant or lactating women, 126 patients with hypersensitivity to study drugs, patients with chronic renal failure with 127 (eGFR<40 mL/min), patients with a history of retinopathy or macular degeneration, 128 known Glucose 6 Phosphate Dehydrogenase (G6PD) deficiency, patients with liver 129 disease, cirrhosis or those using the following medications: colchicine, ergotamine, 144 assignment to study treatment groups and was stratified according to center. 145 Randomization was carried out by one of the investigators who did not participate in . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 159 count of tablets to evaluate therapeutic adherence, and radiography taken at the 160 beginning of the study and on day 11. On day 21 of the follow-up, the participants 161 were called by phone to evaluate symptoms and to investigate whether the patient 162 had returned to routine activities, required hospitalization, or had any of the 163 secondary outcomes. All participants who showed a change suggestive of 164 deterioration (oxygen saturation less than 90% in room air, and shortness of breath 165 or pneumonia) during their digital follow-ups were contacted by a specialized 166 physician to confirm the data and establish the behavior to follow. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 16, 2022. ; https://doi.org/10.1101/2022.04.06.22273531 doi: medRxiv preprint . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 16, 2022. ; https://doi.org/10.1101/2022.04.06.22273531 doi: medRxiv preprint . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 16, 2022. ; https://doi.org/10.1101/2022.04.06.22273531 doi: medRxiv preprint Impact of Azithromycin and/or Hydroxychloroquine on Hospital Mortality in COVID-402 19 Natural history of COVID-19 and therapeutic 406 options Examination of patient characteristics and hydroxychloroquine use based on the 409 US Food and Drug Administration's recommendation: a cross-sectional analysis in 410 New York Lineamiento estandarizado para la vigilancia 412 epidemiológica y por laboratorio de COVID-19" aprobado por el Comité Nacional 413 para la Vigilancia Epidemiológica (CONAVE) U-shaped-aggressiveness of SARS-CoV-2: Period between initial 416 symptoms and clinical progression to COVID-19 suspicion. A population-based 417 cohort study Clinical research IV. 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