Safety and Efficacy of Hydroxychloroquine Associated With Azithromycin in SARS-Cov-2 Virus (COVID-19)

The current pandemic associated with coronavirus disease 2019 (COVID-19) represents a major
global health challenge. There are no effective therapies for the management of COVID-19 that
have been proven to improve clinical outcomes in this high-risk group of patients.
Hydroxychloroquine and its combination with azithromycin have been suggested to improve viral
clearance, but its effect on clinical outcomes remains uncertain.

This is an open-label pragmatic multicentre randomized (concealed) clinical trial of 7 days
of hydroxychloroquine (400 mg BID) plus azithromycin (500 mg once daily), hydroxychloroquine
400 mg BID, or standard of care for moderately severe hospitalized patients with suspected or
confirmed COVID-19 (in-patients with up to 4L/minute oxygen supply through nasal catheter).
Patients are randomized in around 50 recruiting sites (630 patients with confirmed COVID-19;
1:1:1; 210 patients per arm).

The primary endpoint is a 7-level ordinal scale measured at 15-days: 1) not hospitalized,
without limitations on activities; 2) not hospitalized, with limitations on activities; 3)
hospitalized, not using supplementary oxygen; 4) hospitalized, using supplementary oxygen; 5)
hospitalized, using high-flow nasal cannula or non-invasive ventilation; 6) hospitalized, on
mechanical ventilation; 7) death. Secondary endpoints are the ordinal scale at 7 days, need
for mechanical ventilation and rescue therapies during 15 days, need of high-flow nasal
cannula or non-invasive ventilation during 15 days, length of hospital stay, in-hospital
mortality, thromboembolic events, occurrence of acute kidney injury, defined as an increase
in creatinine above 1.5 times the baseline value and number of days free of respiratory
support at 15 days. Secondary safety outcomes include prolongation of QT interval on
electrocardiogram, ventricular arrhythmias, and liver toxicity. The main analysis will
consider all patients with confirmed COVID-19 in the groups they were randomly assigned.