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.
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.
Drug: 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.
Other Name: HCQ+AZI
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.
Other Name: HCQ
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
Hospital de Urgência e Emergência de Rio Branco
Rio Branco, AC, Brazil
Hospital e Clínica São Roque
Ipiaú, BA, Brazil
Hospital da Cidade
Salvador, BA, Brazil
Hospital Maternidade São Vicente de Paulo
Barbalha, CE, Brazil
Hospital de Messejana Dr. Carlos Alberto Studart Gomes
Fortaleza, CE, Brazil
Hospital Unimed Cariri
Juazeiro Do Norte, CE, Brazil
Hospital Brasilia
Brasilia, DF, Brazil
Hospital Estadual Jayme dos Santos Neves
Serra, ES, Brazil
Hospital Evangélico de Vila Velha
Vila Velha, ES, Brazil
Secretaria de Estado de Saúde de Goias
Goiânia, GO, Brazil
Santa Casa de Misericórdia de Belo Horizonte Santa Casa de BH
Belo Horizonte, MG, Brazil
Hospital Santa Paula
Passos, MG, Brazil
Santa Casa da Misericordia - UTI (São João Del Rey)
São João Del Rei, MG, Brazil
Hospital Maternidade E Pronto Socorro Santa Lucia Ltda
Poços De Caldas, Minas Gerais, Brazil
Universidade Estadual de Londrina
Londrina, Paraná, Brazil
Hospital Adventista de Belém
Belém, Pará, Brazil
Hospital Adventista de Belem
Belem, PA, Brazil
Procape - Pronto S.Cardiologico de Pe.Prof.Luiz Tavares-
Recife, PE, Brazil
Liga Paranaense de Combate ao Câncer
Curitiba, PR, Brazil
Hospital Giselda Trigueiro
Natal, Rio Grande Do Norte, 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
Hospital Naval Marcílio Dias
Rio de Janeiro, RJ, Brazil
Hospital São Lucas
Rio De Janeiro, RJ, Brazil
Hospital Maternidade PROMATER
Natal, RN, Brazil
Associação Dr. Bartholomeu Tacchini
Bento Gonçalves, RS, Brazil
Hospital Geral de Caxias do Sul
Caxias Do Sul, RS, Brazil
Hospital Bruno Born
Lajeado, RS, Brazil
Hospital São Vicente de Paulo
Passo Fundo, RS, 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, SC, Brazil
Hospital Universitário Polydoro Ernani de São Thiago/HU - UFSC
Florianópolis, SC, Brazil
Centro Hospitalar Unimed
Joinville, SC, Brazil
Hospital Dona Helena
Joinville, SC, Brazil
Hospital Municipal Sao Jose
Joinville, SC, Brazil
Hospital Regional Hans Dieter Schmidt
Joinville, SC, Brazil
Faculdade de Medicina de Botucatu
Botucatu, SP, Brazil
nstituto de Pesquisa Clínica de Campinas
Campinas, SP, Brazil
Fundação do ABC (Hospital Estadual Mário Covas)
Santo André, SP, Brazil
AC Camargo Cancer Center - Fundação Antonio Prudente
São Paulo, SP, Brazil
Casa de Saude Santa Marcelina
São Paulo, SP, Brazil
Hospital Alemão Oswaldo Cruz
São Paulo, SP, Brazil
Hospital Moriah
São Paulo, SP, Brazil
Hospital Nove de Julho
São Paulo, SP, Brazil
Hospital Santa Paula
São Paulo, SP, Brazil
Hospital São Camilo Pompeia
São Paulo, SP, Brazil
Fundação Pio XII
Barretos, 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
Otávio Berwanger, PhD, Study Director
Hospital Israelita Albert Einstein