An Open-label, Randomized Controlled Trial of Hydroxychloroquine and Azithromycin for COVID-19 Infection on Hospitalized, Noncritical Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 667
- 试验地点
- 28
- 主要终点
- Evaluation of the clinical status
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with suspected or confirmed COVID-19 admitted to inpatient units and intensive care units
排除标准
- •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
研究组 & 干预措施
Hydroxychloroquine
Hydroxychloroquine after randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] for 07 days.
干预措施: Hydroxychloroquine Oral Product (Drug)
Hydroxychloroquine + azithromycin
Hydroxychloroquine + azithromycin. After randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] + azithromycin [500mg 1x/day]) for 07 days.
干预措施: Hydroxychloroquine + azithromycin (Drug)
结局指标
主要结局
Evaluation of the clinical status
时间窗: 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
次要结局
- Hospital Length of Stay(28 days after randomization)
- Use of non-invasive ventilation(7 days after randomization)
- Thromboembolic complications(15 days after randomization)
- Use of mechanical ventilation during hospital stay(15 days after randomization)
- Ordinal scale in 7 days(7 days after randomization)
- Need of intubation and mechanical ventilation(7 days after randomization)
- All-cause mortality(28 days after randomization)
- Acute renal disfunction(15 days after randomization)
- Number of days alive and free of respiratory support up to 15 days(15 days)