azithromycin plus hydroxychloroquine (n=61) vs. placebo (n=56)
randomized controlled trial
Hydroxychloroquine plus azithromycin
500 mg daily azithromycin for 3 days followed by 250 mg daily azithromycin for 12 days combined with 200 mg twice daily hydroxychloroquine for all 15 days.
Placebo/Placebo
Matching placebo capsules
All patients in both groups received standard assessment and treatment is based on organ supportive therapy such as oxygen therapy (central), fluid therapy, antibiotic therapy for secondary infections. If the disease progress to severe acute respiratory failure, the patients will often require referral to an intensive care unit for mechanical ventilation.
COVID 19 hospitalized
Patients ≥18 years, admitted to hospital for ≤48 h (not intensive care) with a positive SARS-CoV-2 RT-PCR test. Patients receiving more than 5 L oxygen supply were excluded.
Double-blind.
Multicenter; 6 hospitals in Denmark.
Phase 2.
After randomisation of 117 patients (50%), at the first planned interim analysis, the data and safety monitoring board recommended stopping enrolment due to futility, based on pre-specified criteria.
Coalition Covid-19 Brazil I (Cavalcanti) - HCQ AZI, 2020 NCT04322123
azithromycin plus hydroxychloroquine (n=217) vs. standard of care (n=227)
randomized controlled trial
Hydroxychloroquine plus azithromycin
Standard of care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days.
Standard of care
The use of glucocorticoids, other immunomodulators, antibiotic agents, and antiviral agents was allowed.
3 arms: hydroxychloroquine plus azythromycin, hydroxychloroquine monotherapy and standard of care (1:1:1 ratio). All patients received standard of care.
COVID-19 mild to moderate
Adult patients (18 years and older) with suspected or confirmed COVID-19 admitted to inpatients units and intensive care units. Patients using non-invasive ventilation or invasive mechanical ventilation were excluded. Patients with previous use of chloroquine, hydroxychloroquine, azithromycin or any other macrolide for more than 24h before enrollment were excluded.
Open-label.
Multicenter; 55 sites in Brazil.
Scores on the scale were defined as follows: a score of 1 indicated not hospitalized with no limitations on activities; 2, not hospitalized but with limitations on activities; 3, hospitalized and not receiving supplemental oxygen; 4,hospitalized and receiving supplemental oxygen;5, hospitalized and receiving oxygen supplementation administered by a high-flow nasal cannula or noninvasive ventilation; 6, hospitalized and receiving mechanical ventilation; and 7, death.
3 interim analyses planned, only the first one was conducted.
