Background Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. Methods We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. Results A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P=1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P=1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent. Conclusions Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123 .)

clinicaltrials.gov Identifier: NCT01374022.

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pecially acute coronary syndromes (ACS), are the leading cause of morbidity and mortality globally. 1,2 Large-scale randomized trials have established the efficacy of several interventions for the care of patients with ACS, including antiplatelet therapy, anticoagulation, reperfusion for patients with STsegment elevation myocardial infarction (STEMI), and secondary prevention with aspirin, ␤-blockers, statins, and angiotensin-converting enzyme inhibitors. 3-8 Nevertheless, registries have consistently demonstrated that the translation of research findings into practice is suboptimal 9-11 and that these care gaps are even greater in low-and middle-income countries. 12-15 Changing clinical behavior to improve quality of care is challenging. Prior systematic reviews have suggested that certain quality improvement (QI) tools are associated with better quality of care. 16 These include reminders, educational outreach visits, audit and feedback, case management, and distribution of edu-Author Affiliations and the BRIDGE-ACS Investigators are listed at the end of this article.

clinicaltrials.gov Identifier: NCT01448642.