Safety and Efficacy of Hydroxychloroquine Associated With Azithromycin in SARS-Cov-2 Virus (COVID-19) (Coalition-I)
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| ClinicalTrials.gov Identifier: NCT04322123 |
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Recruitment Status :
Completed
First Posted : March 26, 2020
Last Update Posted : April 5, 2022
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Coronavirus Infections | Drug: Hydroxychloroquine Oral Product Drug: Hydroxychloroquine + azithromycin | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 667 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | An Open-label, Randomized Controlled Trial of Hydroxychloroquine and Azithromycin for COVID-19 Infection on Hospitalized, Noncritical Patients |
| Actual Study Start Date : | April 1, 2020 |
| Actual Primary Completion Date : | June 2, 2020 |
| Actual Study Completion Date : | June 2, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Hydroxychloroquine
Hydroxychloroquine after randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] for 07 days.
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Drug: Hydroxychloroquine Oral Product
Hydroxychloroquine 400 mg BID |
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Experimental: Hydroxychloroquine + azithromycin
Hydroxychloroquine + azithromycin. After randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] + azithromycin [500mg 1x/day]) for 07 days.
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Drug: Hydroxychloroquine + azithromycin
Hydroxychloroquine 400 mg BID + azithromycin 500 mg once a day |
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No Intervention: Control
standard treatment protocol for 2019-nCoV infection.
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- Evaluation of the clinical status [ Time Frame: 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.
- Alive at home without limitations on activities
- Alive at home without limitations on activities
- In the hospital without oxygen
- In the hospital using oxygen
- In the hospital using high-flow nasal catheter or non-invasive ventilation
- In hospital, on mechanical ventilation
- Dead
- Ordinal scale in 7 days [ Time Frame: 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.
- Alive at home without limitations on activities
- Alive at home without limitations on activities
- In the hospital without oxygen
- In the hospital using oxygen
- In the hospital using high-flow nasal catheter or non-invasive ventilation
- In hospital, on mechanical ventilation
- Dead
- Need of intubation and mechanical ventilation [ Time Frame: 7 days after randomization ]Need of intubation and mechanical ventilation up to the 7th day after randomization
- Use of mechanical ventilation during hospital stay [ Time Frame: 15 days after randomization ]Use of mechanical ventilation during hospital stay
- Use of non-invasive ventilation [ Time Frame: 7 days after randomization ]Use of non-invasive ventilation up to the 7th day after randomization
- Hospital Length of Stay [ Time Frame: 28 days after randomization ]Hospital Length of Stay
- All-cause mortality [ Time Frame: 28 days after randomization ]All-cause mortality rates during hospital stay
- Thromboembolic complications [ Time Frame: 15 days after randomization ]
Occurrence of thromboembolic complications such as:
Deep vein thrombosis Pulmonary Embolism Stroke
- Acute renal disfunction [ Time Frame: 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 [ Time Frame: 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.
- Safety outcome on corrected QT interval [ Time Frame: At day 3 and 7 after enrollment ]Corrected QT interval
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04322123
Show 28 study locations
| Study Chair: | Alexandre Biasi, PhD | Hospital do Coração | |
| Principal Investigator: | Otavio Berwanger | Hospital Israelita Albert Einstein |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Hospital do Coracao |
| ClinicalTrials.gov Identifier: | NCT04322123 |
| Other Study ID Numbers: |
Brazil COVID Coalition I Trial |
| First Posted: | March 26, 2020 Key Record Dates |
| Last Update Posted: | April 5, 2022 |
| Last Verified: | April 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Coronavirus Infections Coronaviridae Infections Hydroxychloroquine Infections Nidovirales Infections RNA Virus Infections Virus Diseases Azithromycin |
Anti-Bacterial Agents Anti-Infective Agents Antimalarials Antiprotozoal Agents Antiparasitic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antirheumatic Agents |