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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04322123
Recruitment Status : Active, not recruiting
First Posted : March 26, 2020
Last Update Posted : June 1, 2020
Sponsor:
Collaborators:
Hospital Israelita Albert Einstein
Hospital Sirio-Libanes
Brazilian Research In Intensive Care Network
EMS
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Coronavirus Infections Drug: Hydroxychloroquine Oral Product Drug: Hydroxychloroquine + azithromycin Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 630 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
Estimated Primary Completion Date : August 30, 2020
Estimated Study Completion Date : August 30, 2020


Arm Intervention/treatment
Experimental: Hydroxychloroquine
Hydroxychloroquine after randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] for 07 days.
Drug: Hydroxychloroquine Oral Product
Hydroxychloroquine 400 mg BID

Experimental: Hydroxychloroquine + azithromycin
Hydroxychloroquine + azithromycin. After randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] + azithromycin [500mg 1x/day]) for 07 days.
Drug: Hydroxychloroquine + azithromycin
Hydroxychloroquine 400 mg BID + azithromycin 500 mg once a day

No Intervention: Control
standard treatment protocol for 2019-nCoV infection.



Primary Outcome Measures :
  1. 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.

    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 :
  1. 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.

    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

  2. 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

  3. Use of mechanical ventilation during hospital stay [ Time Frame: 15 days after randomization ]
    Use of mechanical ventilation during hospital stay

  4. Use of non-invasive ventilation [ Time Frame: 7 days after randomization ]
    Use of non-invasive ventilation up to the 7th day after randomization

  5. Hospital Length of Stay [ Time Frame: 28 days after randomization ]
    Hospital Length of Stay

  6. All-cause mortality [ Time Frame: 28 days after randomization ]
    All-cause mortality rates during hospital stay

  7. Thromboembolic complications [ Time Frame: 15 days after randomization ]

    Occurrence of thromboembolic complications such as:

    Deep vein thrombosis Pulmonary Embolism Stroke


  8. 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

  9. 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.


Other Outcome Measures:
  1. Safety outcome on corrected QT interval [ Time Frame: At day 3 and 7 after enrollment ]
    Corrected QT interval



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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


Locations
Show Show 28 study locations
Sponsors and Collaborators
Hospital do Coracao
Hospital Israelita Albert Einstein
Hospital Sirio-Libanes
Brazilian Research In Intensive Care Network
EMS
Investigators
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Study Chair: Alexandre Biasi, PhD Hospital do Coração
Principal Investigator: Otavio Berwanger Hospital Israelita Albert Einstein
Study Data/Documents: Study Protocol  This link exits the ClinicalTrials.gov site
Preprint of the Protocol

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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: June 1, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infection
Coronavirus Infections
Severe Acute Respiratory Syndrome
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Azithromycin
Hydroxychloroquine
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents