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

April 3, 2022 updated by: Hospital do Coracao

An Open-label, Randomized Controlled Trial of Hydroxychloroquine and Azithromycin for COVID-19 Infection on Hospitalized, Noncritical Patients

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
667

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • BA
      • Feira De Santana, BA, Brazil
        • Hospital Geral Clériston Andrade
      • Salvador, BA, Brazil
        • Hospital Ana Nery - HAN/SESAB
      • Vitória Da Conquista, BA, Brazil
        • HHospital SAMUR
      • Vitória Da Conquista, BA, Brazil
        • Hospital Geral de Vitória da Conquista
    • DF
      • Brasilia, DF, Brazil
        • Hospital de Brasília
      • Brasília, DF, Brazil
        • Instituto de Cardiologia do Distrito Federal
    • ES
      • Colatina, ES, Brazil
        • Hospital Maternidade São José - UNESC - Fundação Social Rural de Colatina
    • MG
      • Nova Lima, MG, Brazil
        • Hospital Vila da Serra
      • São João Del Rei, MG, Brazil
        • Santa Casa de Misericórdia de São João del Rei
    • PR
      • Londrina, PR, Brazil
        • Associação Evangélica Beneficente de Londrina - Hospital Evangélico de Londrina
    • RJ
      • Rio De Janeiro, RJ, Brazil
        • Instituto Estadual Do Cerebro Paulo Niemeyer
    • RS
      • Caxias do Sul, RS, Brazil
        • Hospital Geral de Caxias do Sul
      • Porto Alegre, RS, Brazil
        • Hospital Santa Rita - Irmandade Santa Casa de Porto Alegre
      • Porto Alegre, RS, Brazil
        • Hospital São Francisco - Irmandade Santa Casa de Porto Alegre
    • S
      • São Paulo, S, Brazil
        • Hospital SEPACO
    • SC
      • Criciuma, SC, Brazil
        • Hospital São José
      • Florianópolis, SC, Brazil
        • Hospital Baía Sul - Baía Sul Medical Center
      • Joinville, SC, Brazil
        • Centro Hospitalar Unimed
    • SP
      • Barretos, SP, Brazil
        • Hospital de Amor - Unidade Barretos (Fundação PIO XII)
      • São Paulo, SP, Brazil
        • Hospital São Paulo - UNIFESP
      • São Paulo, SP, Brazil
        • Casa de Saúde Santa Marcelina
      • São Paulo, SP, Brazil
        • Hospital Albert Einstein
      • 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 Sirio-Libanes
    • Sc
      • Florianópolis, Sc, Brazil
        • Hospital Nereu Ramos

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
15 days after randomization

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
7 days after randomization
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
7 days after randomization
Use of mechanical ventilation during hospital stay
Time Frame: 15 days after randomization
Use of mechanical ventilation during hospital stay
15 days after randomization
Use of non-invasive ventilation
Time Frame: 7 days after randomization
Use of non-invasive ventilation up to the 7th day after randomization
7 days after randomization
Hospital Length of Stay
Time Frame: 28 days after randomization
Hospital Length of Stay
28 days after randomization
All-cause mortality
Time Frame: 28 days after randomization
All-cause mortality rates during hospital stay
28 days after randomization
Thromboembolic complications
Time Frame: 15 days after randomization

Occurrence of thromboembolic complications such as:

Deep vein thrombosis Pulmonary Embolism Stroke
15 days after randomization
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
15 days after randomization
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.
15 days

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety outcome on corrected QT interval
Time Frame: At day 3 and 7 after enrollment
Corrected QT interval
At day 3 and 7 after enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hospital do Coracao

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Hospital Israelita Albert Einstein
Hospital Sirio-Libanes
Brazilian Research In Intensive Care Network
EMS

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Alexandre Biasi, PhD, Hospital do Coracao
  • Principal Investigator: Otavio Berwanger, Hospital Israelita Albert Einstein

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 2, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 2, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 24, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 26, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 5, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 3, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Brazil COVID Coalition I Trial

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Study Data/Documents

  1. Study Protocol
    Information comments: Preprint of the Protocol

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings