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

Hospital do Coracao

Status and phase: Completed; Phase 3

Conditions: Coronavirus Infections

Treatments: Drug: Hydroxychloroquine + azithromycin; Drug: Hydroxychloroquine Oral Product

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT04322123

Brazil COVID Coalition I Trial

Details and patient eligibility

About

Coronavirus (COVID-19) is a somewhat new and recognized infectious disease that is now spreading to several countries in the world, including Brazil. Hydroxychloroquine and azithromycin may be useful for treating those patients.

COALITION I study aims to compared standard of care, hydroxychloroquine plus azithromycin and hydroxychloroquine monotherapy for treatment of hospitalized patients with COVID-19.

COALITION I will recruit 630 patients with infection by COVID-19 (210 per arm). Ordinal endpoint of status at 15 days will be the primary endpoint.

Full description

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.

Enrollment: 667 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with suspected or confirmed COVID-19 admitted to inpatient units and intensive care units

Exclusion criteria

• Need for oxygen supplementation > 4 litters per min
• Patients using a high-flow nasal catheter
• Patients using non-invasive mechanical ventilation
• Patients using invasive mechanical ventilation
• Males and females aged < 18 years
• Pregnancy
• Allergy to chloroquine or derivatives
• Allergy to azithromycin
• Patients that have already received more than one dose of either azithromycin or hydroxychloroquine before enrollment
• Patients with respiratory symptoms for more than 14 days

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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667 participants in 3 patient groups

Hydroxychloroquine

Experimental group

Description:

Hydroxychloroquine after randomization, Hydroxychloroquine \[400mg 2x/day, 12/12h\] for 07 days.

Treatment:

Drug: Hydroxychloroquine Oral Product

Hydroxychloroquine + azithromycin

Experimental group

Description:

Hydroxychloroquine + azithromycin. After randomization, Hydroxychloroquine \[400mg 2x/day, 12/12h\] + azithromycin \[500mg 1x/day\]) for 07 days.

Treatment:

Drug: Hydroxychloroquine + azithromycin

Control

No Intervention group

Description:

standard treatment protocol for 2019-nCoV infection.