Hydroxychloroquine alone or in combination with azithromycin to prevent major clinical events in hospitalised patients with coronavirus infection (COVID-19): rationale and design of a randomised, controlled clinical trial

摘要: Abstract Introduction Hydroxychloroquine and its combination with azithromycin have been suggested to improve viral clearance in patients COVID-19, but effect on clinical outcomes remains uncertain. Methods analysis We describe the rationale design of an open-label pragmatic multicentre randomised (concealed) trial 7 days hydroxychloroquine (400 mg BID) plus (500 once daily), 400 BID, or standard care for moderately severe hospitalised suspected confirmed COVID-19 (in-patients up 4L/minute oxygen supply through nasal catheter). Patients are around 50 recruiting sites we plan enrol 630 COVID-19. The primary endpoint is a 7-level ordinal scale measured at 15-days: 1)not hospitalised, without limitations activities; 2)not 3)hospitalised, not using supplementary oxygen; 4)hospitalised, 5)hospitalised, high-flow cannula non-invasive ventilation; 6)hospitalised, mechanical 7)death. Secondary endpoints days, need ventilation rescue therapies during 15 length hospital stay, in-hospital mortality, thromboembolic events, occurrence acute kidney injury, number free respiratory support days. safety include prolongation QT interval electrocardiogram, ventricular arrhythmias, liver toxicity. main will consider all groups they were randomly assigned. Ethics dissemination This study has approved by Brazil’s National Ethic Committee (CONEP) Health Surveillance Agency (ANVISA). An independent data monitoring committee perform interim analyses evaluate adverse events throughout trial. Results be submitted publication after enrolment follow-up complete, as well presented reported local health agencies. ClinicalTrials.gov identifier NCT04322123 Strengths this Pragmatic controlled azithromycin, in-patients Multicentre: Brazil planned (1:1:1) ([1] [2] [3] [4] [5] [6] [7] death) Open label (no placebo)