AzTrials
AzTrials

Coronavirus InfectionsPhase 3NCT04321278

Safety and Efficacy of Hydroxychloroquine Associated With Azithromycin in SARS-CoV2 Virus (Coalition Covid-19 Brasil II)

A Phase 3 study testing Hydroxychloroquine + azithromycin and Hydroxychloroquine in people with Coronavirus Infections and Pneumonia, Viral, run by Hospital Israelita Albert Einstein at 58 sites in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract. Around 20% of those infected have severe pneumonia and currently there is no specific or effective therapy to treat this disease. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Coronavirus Infections, Pneumonia, Viral
What is being tested?
Hydroxychloroquine + azithromycin and Hydroxychloroquine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
440 participants
Where
58 sitesBrazil
Study dates
28 Mar 2020to 14 Jun 2020
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males and females aged > 18 years;
  • Suspected or confirmed infection by SARS-CoV2;
  • Presenting with one of the following:
  • Need for oxygen supplementation > 4 L/min, or
  • Need for high-flow nasal canula, or
  • Need for non-invasive ventilation, or
  • Need for mechanical ventilation.

Who cannot join

  • Refusal to provide written informed consent (either the patient or a legal representative);
  • Hypersensitivity to any of the drugs used in the study (Azithromycin or Hydroxychloroquine);
  • Patients with more than 48 hours of prior study medication use;
  • Patients with onset of symptoms longer than 14 days;
  • Patients with long QT syndrome or severe ventricular arrhythmias, not protected by an implantable cardioverter defibrillators (ICD).;
  • QTc>= 480ms;
Show all 13Show fewer
  • Do not resuscitate order or exclusive palliative care;
  • Patients with liver disease or cirrhosis or abnormal liver enzyme tests above three times the upper limit values (alanine aminotransferase -ALT and aspartate aminotransferase - AST);
  • Patients with known retinopathy or macular degeneration;
  • Patients with history of pancreatitis;
  • Patients with concomitant use of medications that alter the absorption or excretion of azithromycin or hydroxychloroquine;
  • Breastfeeding women;
  • Pregnancy

Trial locations and contacts

58 sites in 1 country.

58 sites in 1 country

Brazil58 sites

  • Hospital Maternidade São Vicente de Paulo

    Barbalha, Ceará

  • Fundação Pio XII

    Barretos, São Paulo

  • Hospital Adventista de Belem

    Belém, Pará

  • Hospital Adventista de Belém

    Belém, Pará

  • Santa Casa de Misericórdia de Belo Horizonte Santa Casa de BH

    Belo Horizonte, Minas Gerais

  • Associação Dr. Bartholomeu Tacchini

    Bento Gonçalves, Rio Grande do Sul

  • Maestri E Kormann Consultoria Medico-Cientifica

    Blumenau, Santa Catarina

  • Faculdade de Medicina de Botucatu

    Botucatu, São Paulo

  • Hospital Brasilia

    Brasília, Federal District

  • nstituto de Pesquisa Clínica de Campinas

    Campinas, São Paulo

  • Hospital Geral de Caxias do Sul

    Caxias do Sul, Rio Grande do Sul

  • Sociedade Literaria e Caritativa Santo Agostinho

    Criciúma, Santa Catarina

  • Liga Paranaense de Combate ao Câncer

    Curitiba, Paraná

  • Hospital Nereu Ramos

    Florianópolis, Santa Catarina

  • Hospital Universitário Polydoro Ernani de São Thiago/HU - UFSC

    Florianópolis, Santa Catarina

  • Hospital de Messejana Dr. Carlos Alberto Studart Gomes

    Fortaleza, Ceará

  • Secretaria de Estado de Saúde de Goias

    Goiânia, Goiás

  • Hospital e Clínica São Roque

    Ipiaú, Estado de Bahia

  • Centro Hospitalar Unimed

    Joinville, Santa Catarina

  • Hospital Dona Helena

    Joinville, Santa Catarina

  • Hospital Municipal Sao Jose

    Joinville, Santa Catarina

  • Hospital Regional Hans Dieter Schmidt

    Joinville, Santa Catarina

  • Hospital Unimed Cariri

    Juazeiro do Norte, Ceará

  • Hospital Bruno Born

    Lajeado, Rio Grande do Sul

  • Universidade Estadual de Londrina

    Londrina, Paraná

  • Hospital Giselda Trigueiro

    Natal, Rio Grande do Norte

  • Hospital Maternidade PROMATER

    Natal, Rio Grande do Norte

  • Hospital São Vicente de Paulo

    Passo Fundo, Rio Grande do Sul

  • Hospital Santa Paula

    Passos, Minas Gerais

  • Hospital Maternidade E Pronto Socorro Santa Lucia Ltda

    Poços de Caldas, Minas Gerais

  • Hospital Moinhos de Vento

    Porto Alegre, Rio Grande do Sul

  • Irmandade da Santa Casa de Misericordia de Porto Alegre

    Porto Alegre, Rio Grande do Sul

  • Procape - Pronto S.Cardiologico de Pe.Prof.Luiz Tavares-

    Recife, Pernambuco

  • Hospital de Urgência e Emergência de Rio Branco

    Rio Branco, Acre

  • Hospital Naval Marcílio Dias

    Rio de Janeiro, Rio de Janeiro

  • Hospital São Lucas

    Rio de Janeiro, Rio de Janeiro

  • Hospital da Cidade

    Salvador, Estado de Bahia

  • Fundação do ABC (Hospital Estadual Mário Covas)

    Santo André, São Paulo

  • Santa Casa da Misericordia - UTI (São João Del Rey)

    São João del Rei, Minas Gerais

  • AC Camargo Cancer Center - Fundação Antonio Prudente

    São Paulo, São Paulo

  • Casa de Saude Santa Marcelina

    São Paulo, São Paulo

  • Hospital Alemão Oswaldo Cruz

    São Paulo, São Paulo

  • Hospital Moriah

    São Paulo, São Paulo

  • Hospital Nove de Julho

    São Paulo, São Paulo

  • Hospital Santa Paula

    São Paulo, São Paulo

  • Hospital São Camilo Pompeia

    São Paulo, São Paulo

  • Hospital Israelita Albert Einstein

    São Paulo, 05652-900

  • A Beneficência Portuguesa de São Paulo - BP

    São Paulo

  • Associacao Beneficente Siria

    São Paulo

  • Hospital Vila Santa Catarina

    São Paulo

  • Real e Benemérita Associação Portuguesa de Beneficência/SP - 1

    São Paulo

  • Secretaria de Saúde do Estado de São Paulo

    São Paulo

  • Serv Social da Industria do papel, papelão e cortiça do estado de SP

    São Paulo

  • Sociedade Beneficente de Senhoras Hospital Sírio-Libanês

    São Paulo

  • Universidade Federal de São Paulo

    São Paulo

  • Hospital Estadual Jayme dos Santos Neves

    Serra, Espírito Santo

  • Hospital Evangélico de Vila Velha

    Vila Velha, Espírito Santo

  • Santa Casa de Misericordia de Votuporanga

    Votuporanga, São Paulo

Other trials in Brazil

About this study

Official title: Evaluation of the Safety and Clinical Efficacy of Hydroxychloroquine Associated With Azithromycin in Patients With Pneumonia Caused by Infection by the SARS-CoV2 Virus - Coalition COVID-19 Brasil II - SEVERE - Patients

The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract. Around 20% of those infected have severe pneumonia and currently there is no specific or effective therapy to treat this disease. Therapeutic options using malaria drugs chloroquine and hydroxychloroquine have shown promising results in vitro and in vivo test. But those efforts have not involved large, carefully-conducted controlled studies that would provide the global medical community the proof that these drugs work on a significant scale. In this way, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in patients hospitalized with pneumonia by SARS-CoV2 virus.

Read the detailed description

The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract that is now spreading to several countries in the world, including Brazil. Mortality rates after infection are higher in adults over 60 and with a history of comorbidities. The most serious patients need care in intensive care units (ICU). Most of the time they depend on mechanical ventilation support due to acute respiratory distress syndrome (ARDS). Infection rates are higher than the capacity for intensive care, which represents a serious problem in medical care. Around 20% of those infected have severe pneumonia and so far it does not have a specific therapy, or even, an effective clinical management. Therapeutic options using malaria drugs chloroquine and hydroxychloroquine have shown promising results in vitro and in vivo test. A recent, small, non-randomized study with hydroxychloroquine in 36 patients infected with SARS-Cov-2 proved to be promising in the ability to reset the viral load in 6 days after starting treatment. Thus, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in the clinical evolution by the ordinal scale of 6 points in adult patients hospitalized with pneumonia caused by infection by the SARS-CoV2 virus in Brazil.

Being tested
Hydroxychloroquine + azithromycin, Hydroxychloroquine
Keywords
SARS-CoV2 virus, 2019-nCOV, COVID-19, hydroxychloroquine, azithromycin
Medical subject headings
Coronavirus Infections, Pneumonia, Viral, COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hydroxychloroquine + azithromycinDrug

    Also called HCQ+AZI

    Intervention Group: Hydroxychloroquine + azithromycin. After randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] + azithromycin [500mg 1x/day]) for 10 days. Standard treatment is according to the treatment protocol for 2019-nCoV infection.

  • HydroxychloroquineDrug

    Also called HCQ

    Active Control Group: Hydroxychloroquine. After randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] for 10 days. Standard treatment is according to the treatment protocol for 2019-nCoV infection.

Study groups in NCT04321278
Study groupRoleWhat they receive
Hydroxychloroquine + azithromycinExperimentalHydroxychloroquine [400mg 2x/day, 12/12h] + azithromycin [500mg 1x/day]
Receives: Drug: Hydroxychloroquine + azithromycin
HydroxychloroquineActive comparatorHydroxychloroquine [400mg 2x/day, 12/12h]
Receives: Drug: Hydroxychloroquine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Evaluation of the clinical status

    Evaluation of the clinical status of patients on the 15th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score)

    Measured: 15 days after randomization

Secondary outcomes (9)

  1. All-cause mortality

    All-cause mortality rates at 29 days after randomization

    Measured: 29 days after randomization

  2. Evaluation of the clinical status

    Evaluation of the clinical status of patients on the 7th and 29th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score)

    Measured: 7 and 29 days after randomization

  3. Number of days free from mechanical ventilation

    Number of days free from mechanical ventilation at 29 days after randomization

    Measured: 29 days after randomization

  4. Duration of mechanical ventilation

    Number of days that the patient was on mechanical ventilation after randomization

    Measured: 29 days after randomization

  5. Duration of hospitalization

    Length of hospital stay on survivors

    Measured: 29 days after randomization

  6. Other secondary infections

    Presence of other secondary infections

    Measured: 29 days after randomization

  7. Time from treatment start to death

    Time from treatment start to death

    Measured: 29 days after randomization

  8. Medium and long-term outcomes of SARS-CoV2 infection on morbimortality, daily life activities, mental health, and quality of life

    Morbimortality, daily life activities, mental health, and quality of life

    Measured: 3, 6, 9 and 12 months

  9. Assess whether the tested therapies may be affected by leucocyte phenotype

    Leucocyte transcriptome

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Mar 2020
  2. Study start28 Mar 2020
  3. Primary completion14 Jun 2020
  4. Study completion14 Jun 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
1. Intervention Group: Hydroxychloroquine + azithromycin. After randomization, Hydroxychloroquine \[400mg 2x/day, 12/12h\] + azithromycin \[500mg 1x/day\]) for 10 days. Standard treatment is according to the treatment protocol for 2019-nCoV infection. 2. Active Control Group: Hydroxychloroquine. After randomization, Hydroxychloroquine \[400mg 2x/day, 12/12h\] for 10 days. Standard treatment is according to the treatment protocol for 2019-nCoV infection.
Masking
None (open label)
Enrolment
440 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04321278
Sponsor's protocol ID
30155020.5.1001.0071
Status last verified
Mar 2020
First submitted
23 Mar 2020
Last updated
20 Jan 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Furtado RHM, Barros E Silva PGM, Fonseca HAR, Serpa-Neto A, Correa TD, Guimaraes HP, Pereira AJ, Olivato GB, Zampieri FG, Lisboa T, Junqueira DLM, Lapa MG, Monfardini F, Damiani LP, Echenique LS, Gebara OE, Hoffman Filho CR, Polanczyk CA, Rohde LE, Amazonas R, Machado FR, Avezum A, Azevedo LCP, Veiga VC, Rosa RG, Lopes RD, Cavalcanti AB, Berwanger O; COALITION COVID-19 Brazil Steering Committee and Investigators. Cardiovascular Safety of Azithromycin in Patients Hospitalized With COVID-19: A Prespecified Pooled Analysis of the COALITION I and COALITION II Randomized Clinical Trials. Am J Cardiol. 2024 Mar 1;214:18-24. doi: 10.1016/j.amjcard.2023.11.069. Epub 2023 Dec 15.

    PubMed 38104755

  • Furtado RHM, Berwanger O, Fonseca HA, Correa TD, Ferraz LR, Lapa MG, Zampieri FG, Veiga VC, Azevedo LCP, Rosa RG, Lopes RD, Avezum A, Manoel ALO, Piza FMT, Martins PA, Lisboa TC, Pereira AJ, Olivato GB, Dantas VCS, Milan EP, Gebara OCE, Amazonas RB, Oliveira MB, Soares RVP, Moia DDF, Piano LPA, Castilho K, Momesso RGRAP, Schettino GPP, Rizzo LV, Neto AS, Machado FR, Cavalcanti AB; COALITION COVID-19 Brazil II Investigators. Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial. Lancet. 2020 Oct 3;396(10256):959-967. doi: 10.1016/S0140-6736(20)31862-6. Epub 2020 Sep 5.

    PubMed 32896292

  • Lasheras I, Santabarbara J. Use of antimalarial drugs in the treatment of COVID-19: A window of opportunity? Med Clin (Barc). 2020 Jul 10;155(1):23-25. doi: 10.1016/j.medcli.2020.04.004. Epub 2020 Apr 22. No abstract available. English, Spanish.

    PubMed 32386744

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Hydroxychloroquine + azithromycin and Hydroxychloroquine in people with Coronavirus Infections and Pneumonia, Viral, run by Hospital Israelita Albert Einstein at 58 sites in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluation of the clinical status (time frame: 15 days after randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04321278, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in