Safety and Efficacy of Hydroxychloroquine Associated With Azithromycin in SARS-Cov-2 Virus (COVID-19)
- Conditions
- Coronavirus Infections
- Interventions
- Registration Number
- NCT04322123
- Lead Sponsor
- Hospital do Coracao
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 667
- Patients with suspected or confirmed COVID-19 admitted to inpatient units and intensive care units
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Hydroxychloroquine Hydroxychloroquine Oral Product Hydroxychloroquine after randomization, Hydroxychloroquine \[400mg 2x/day, 12/12h\] for 07 days. Hydroxychloroquine + azithromycin Hydroxychloroquine + azithromycin Hydroxychloroquine + azithromycin. After randomization, Hydroxychloroquine \[400mg 2x/day, 12/12h\] + azithromycin \[500mg 1x/day\]) for 07 days.
- Primary Outcome Measures
Name Time Method Evaluation of the clinical status 15 days after randomization Evaluation of the clinical status of patients on the 15th day after randomization defined by the Ordinal Scale of 7 points.
1. Alive at home without limitations on activities
2. Alive at home without limitations on activities
3. In the hospital without oxygen
4. In the hospital using oxygen
5. In the hospital using high-flow nasal catheter or non-invasive ventilation
6. In hospital, on mechanical ventilation
7. Dead
- Secondary Outcome Measures
Name Time Method Hospital Length of Stay 28 days after randomization Hospital Length of Stay
Use of non-invasive ventilation 7 days after randomization Use of non-invasive ventilation up to the 7th day after randomization
Thromboembolic complications 15 days after randomization Occurrence of thromboembolic complications such as:
Deep vein thrombosis Pulmonary Embolism StrokeUse of mechanical ventilation during hospital stay 15 days after randomization Use of mechanical ventilation during hospital stay
Ordinal scale in 7 days 7 days after randomization Evaluation of the clinical status of patients on the 7th day after randomization defined by the Ordinal Scale of 7 points.
1. Alive at home without limitations on activities
2. Alive at home without limitations on activities
3. In the hospital without oxygen
4. In the hospital using oxygen
5. In the hospital using high-flow nasal catheter or non-invasive ventilation
6. In hospital, on mechanical ventilation
7. DeadNeed of intubation and mechanical ventilation 7 days after randomization Need of intubation and mechanical ventilation up to the 7th day after randomization
All-cause mortality 28 days after randomization All-cause mortality rates during hospital stay
Acute renal disfunction 15 days after randomization Occurrence of renal dysfunction, defined as an increase in creatinine above 1.5 times the baseline value
Number of days alive and free of respiratory support up to 15 days 15 days Number of days alive and free of respiratory support up to 15 days (DAFOR15), defined as the sum of days patients did not require supplementary oxygen, non-invasive ventilation, high-flow nasal catheter neither mechanical ventilation at 15 -days. Patients that perished during the 15-day window will receive zero DAFOR15.
Trial Locations
- Locations (28)
Hospital Geral Clériston Andrade
🇧🇷Feira De Santana, BA, Brazil
Hospital Ana Nery - HAN/SESAB
🇧🇷Salvador, BA, Brazil
HHospital SAMUR
🇧🇷Vitória Da Conquista, BA, Brazil
Hospital Geral de Vitória da Conquista
🇧🇷Vitória Da Conquista, BA, Brazil
Hospital de Brasília
🇧🇷Brasilia, DF, Brazil
Instituto de Cardiologia do Distrito Federal
🇧🇷Brasília, DF, Brazil
Hospital Maternidade São José - UNESC - Fundação Social Rural de Colatina
🇧🇷Colatina, ES, Brazil
Hospital Vila da Serra
🇧🇷Nova Lima, MG, Brazil
Santa Casa de Misericórdia de São João Del Rei
🇧🇷São João Del Rei, MG, Brazil
Associação Evangélica Beneficente de Londrina - Hospital Evangélico de Londrina
🇧🇷Londrina, PR, Brazil
Hospital Geral de Caxias do Sul
🇧🇷Caxias do Sul, RS, Brazil
Instituto Estadual do Cérebro Paulo Niemeyer
🇧🇷Rio De Janeiro, RJ, Brazil
Hospital São José
🇧🇷Criciuma, SC, Brazil
Hospital Santa Rita - Irmandade Santa Casa de Porto Alegre
🇧🇷Porto Alegre, RS, Brazil
Hospital São Francisco - Irmandade Santa Casa de Porto Alegre
🇧🇷Porto Alegre, RS, Brazil
Hospital Baía Sul - Baía Sul Medical Center
🇧🇷Florianópolis, SC, Brazil
Hospital Nereu Ramos
🇧🇷Florianópolis, Sc, Brazil
Hospital de Amor - Unidade Barretos (Fundação PIO XII)
🇧🇷Barretos, SP, Brazil
Hospital Albert Einstein
🇧🇷São Paulo, SP, Brazil
Centro Hospitalar Unimed
🇧🇷Joinville, SC, Brazil
Casa de Saúde Santa Marcelina
🇧🇷São Paulo, SP, Brazil
Hospital Beneficência Portuguesa - Real e Benemérita Associação Portuguesa de Beneficência
🇧🇷São Paulo, SP, Brazil
Hospital BP Mirante - Real e Benemérita
🇧🇷São Paulo, SP, Brazil
Hospital das Clínicas da FMUSP
🇧🇷São Paulo, SP, Brazil
Hospital do Servidor Público Estadual - HSPE - IAMSPE
🇧🇷São Paulo, SP, Brazil
Hospital São Paulo - UNIFESP
🇧🇷São Paulo, SP, Brazil
Hospital Sírio-Libanês
🇧🇷São Paulo, SP, Brazil
Hospital SEPACO
🇧🇷São Paulo, S, Brazil