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

NCT ID: NCT04321278

Last Updated: 2021-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 440 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-28
• Study Completion Date: 2020-06-14

Brief 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. 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.

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.

Conditions

Coronavirus Infections; Pneumonia, Viral

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Hydroxychloroquine + azithromycin

Hydroxychloroquine \[400mg 2x/day, 12/12h\] + azithromycin \[500mg 1x/day\]

Group Type: EXPERIMENTAL

Hydroxychloroquine + azithromycin

Intervention Type: DRUG

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.

Hydroxychloroquine

Hydroxychloroquine \[400mg 2x/day, 12/12h\]

Group Type: ACTIVE_COMPARATOR

Hydroxychloroquine

Intervention Type: DRUG

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.

Interventions

Hydroxychloroquine + azithromycin

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.

Intervention Type: DRUG

Hydroxychloroquine

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.

Intervention Type: DRUG

Other Intervention Names

HCQ+AZI; HCQ

Eligibility Criteria

Inclusion Criteria

1. Males and females aged > 18 years;

2. 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.

Exclusion Criteria

1. Refusal to provide written informed consent (either the patient or a legal representative);

2. Hypersensitivity to any of the drugs used in the study (Azithromycin or Hydroxychloroquine);

3. Patients with more than 48 hours of prior study medication use;

4. Patients with onset of symptoms longer than 14 days;

5. Patients with long QT syndrome or severe ventricular arrhythmias, not protected by an implantable cardioverter defibrillators (ICD).;

6. QTc>= 480ms;

7. Do not resuscitate order or exclusive palliative care;

8. 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);

9. Patients with known retinopathy or macular degeneration;

10. Patients with history of pancreatitis;

11. Patients with concomitant use of medications that alter the absorption or excretion of azithromycin or hydroxychloroquine;

12. Breastfeeding women;

13. Pregnancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EMS

INDUSTRY

Sponsor Role: collaborator

Hospital do Coracao

OTHER

Sponsor Role: collaborator

Hospital Sirio-Libanes

OTHER

Sponsor Role: collaborator

Brazilian Research In Intensive Care Network

NETWORK

Sponsor Role: collaborator

Hospital Israelita Albert Einstein

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Otávio Berwanger, PhD

Role: STUDY_DIRECTOR

Hospital Israelita Albert Einstein

Locations

Hospital de Urgência e Emergência de Rio Branco

Rio Branco, Acre, Brazil

Hospital Maternidade São Vicente de Paulo

Barbalha, Ceará, Brazil

Hospital de Messejana Dr. Carlos Alberto Studart Gomes

Fortaleza, Ceará, Brazil

Hospital Unimed Cariri

Juazeiro do Norte, Ceará, Brazil

Hospital Estadual Jayme dos Santos Neves

Serra, Espírito Santo, Brazil

Hospital Evangélico de Vila Velha

Vila Velha, Espírito Santo, Brazil

Hospital e Clínica São Roque

Ipiaú, Estado de Bahia, Brazil

Hospital da Cidade

Salvador, Estado de Bahia, Brazil

Hospital Brasilia

Brasília, Federal District, Brazil

Secretaria de Estado de Saúde de Goias

Goiânia, Goiás, Brazil

Santa Casa de Misericórdia de Belo Horizonte Santa Casa de BH

Belo Horizonte, Minas Gerais, Brazil

Hospital Santa Paula

Passos, Minas Gerais, Brazil

Hospital Maternidade E Pronto Socorro Santa Lucia Ltda

Poços de Caldas, Minas Gerais, Brazil

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

São João del Rei, Minas Gerais, Brazil

Liga Paranaense de Combate ao Câncer

Curitiba, Paraná, Brazil

Universidade Estadual de Londrina

Londrina, Paraná, Brazil

Hospital Adventista de Belem

Belém, Pará, Brazil

Hospital Adventista de Belém

Belém, Pará, Brazil

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

Recife, Pernambuco, Brazil

Hospital Naval Marcílio Dias

Rio de Janeiro, Rio de Janeiro, Brazil

Hospital São Lucas

Rio de Janeiro, Rio de Janeiro, Brazil

Hospital Giselda Trigueiro

Natal, Rio Grande do Norte, Brazil

Hospital Maternidade PROMATER

Natal, Rio Grande do Norte, Brazil

Associação Dr. Bartholomeu Tacchini

Bento Gonçalves, Rio Grande do Sul, Brazil

Hospital Geral de Caxias do Sul

Caxias do Sul, Rio Grande do Sul, Brazil

Hospital Bruno Born

Lajeado, Rio Grande do Sul, Brazil

Hospital São Vicente de Paulo

Passo Fundo, Rio Grande do Sul, Brazil

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, Brazil

Irmandade da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Maestri E Kormann Consultoria Medico-Cientifica

Blumenau, Santa Catarina, Brazil

Sociedade Literaria e Caritativa Santo Agostinho

Criciúma, Santa Catarina, Brazil

Hospital Nereu Ramos

Florianópolis, Santa Catarina, Brazil

Hospital Universitário Polydoro Ernani de São Thiago/HU - UFSC

Florianópolis, Santa Catarina, Brazil

Centro Hospitalar Unimed

Joinville, Santa Catarina, Brazil

Hospital Dona Helena

Joinville, Santa Catarina, Brazil

Hospital Municipal Sao Jose

Joinville, Santa Catarina, Brazil

Hospital Regional Hans Dieter Schmidt

Joinville, Santa Catarina, Brazil

Fundação Pio XII

Barretos, São Paulo, Brazil

Faculdade de Medicina de Botucatu

Botucatu, São Paulo, Brazil

nstituto de Pesquisa Clínica de Campinas

Campinas, São Paulo, Brazil

Fundação do ABC (Hospital Estadual Mário Covas)

Santo André, São Paulo, Brazil

AC Camargo Cancer Center - Fundação Antonio Prudente

São Paulo, São Paulo, Brazil

Casa de Saude Santa Marcelina

São Paulo, São Paulo, Brazil

Hospital Alemão Oswaldo Cruz

São Paulo, São Paulo, Brazil

Hospital Moriah

São Paulo, São Paulo, Brazil

Hospital Nove de Julho

São Paulo, São Paulo, Brazil

Hospital Santa Paula

São Paulo, São Paulo, Brazil

Hospital São Camilo Pompeia

São Paulo, São Paulo, Brazil

Santa Casa de Misericordia de Votuporanga

Votuporanga, São Paulo, Brazil

Hospital Israelita Albert Einstein

São Paulo, , Brazil

A Beneficência Portuguesa de São Paulo - BP

São Paulo, , Brazil

Associacao Beneficente Siria

São Paulo, , Brazil

Hospital Vila Santa Catarina

São Paulo, , Brazil

Real e Benemérita Associação Portuguesa de Beneficência/SP - 1

São Paulo, , Brazil

Secretaria de Saúde do Estado de São Paulo

São Paulo, , Brazil

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

São Paulo, , Brazil

Sociedade Beneficente de Senhoras Hospital Sírio-Libanês

São Paulo, , Brazil

Universidade Federal de São Paulo

São Paulo, , Brazil

Countries

Brazil

References

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.

Reference Type: DERIVED

PMID: 38104755 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32896292 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32386744 (View on PubMed)

Other Identifiers

30155020.5.1001.0071

Identifier Type: -

Identifier Source: org_study_id