Coronavirus Infections
Conditions
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.
Interventions
DRUGHydroxychloroquine Oral Product
Hydroxychloroquine 400 mg BID
Hydroxychloroquine 400 mg BID + azithromycin 500 mg once a day
Sponsors
Hospital Israelita Albert Einstein
Hospital Sirio-Libanes
Brazilian Research In Intensive Care Network
EMS
Hospital do Coracao
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. Dead |
| Need of intubation and mechanical ventilation | 7 days after randomization | Need of intubation and mechanical ventilation up to the 7th day after randomization |
| Use of mechanical ventilation during hospital stay | 15 days after randomization | Use of mechanical ventilation during hospital stay |
| Use of non-invasive ventilation | 7 days after randomization | Use of non-invasive ventilation up to the 7th day after randomization |
| All-cause mortality | 28 days after randomization | All-cause mortality rates during hospital stay |
| Thromboembolic complications | 15 days after randomization | Occurrence of thromboembolic complications such as: Deep vein thrombosis Pulmonary Embolism Stroke |
| 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. |
| Hospital Length of Stay | 28 days after randomization | Hospital Length of Stay |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety outcome on corrected QT interval | At day 3 and 7 after enrollment | Corrected QT interval |
Countries
Brazil
Outcome results
None listed